JournalTOCs

Clinical & Experimental Metastasis
Journal Prestige (SJR): 1.397

Citation Impact (citeScore): 3
Number of Followers: 0

Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0262-0898 - ISSN (Online) 1573-7276
Published by Springer-Verlag

[2626 journals]

Molecules in metastasis
- PubDate: 2019-03-18
  DOI: 10.1007/s10585-019-09962-5
Circulating microRNAs in head and neck cancer: a scoping review of methods
- Abstract: Circulating microRNAs have been described as head and neck cancer biomarkers in multiple anatomical subsites including the oral cavity, nasopharynx, larynx, salivary glands and the skin. While there is an expanding volume of published literature showing the significance of individual or panels of microRNAs, the clinical validation of candidate biomarkers is lacking. The various methods used to collect, store, process and interpret these microRNAs are likely introducing bias and contributing to the inconsistent results. A systematic scoping review was conducted using PRISMA standards to identify published English literature between 2007 and 2018. Pubmed and EMBASE databases were searched using specific keyword combinations related to head and neck cancer, circulating samples (whole blood, plasma or serum) and microRNA. Following the title and abstract review, two primary authors appraised the articles for their suitability to include in the review based on the detail of methodological descriptions. Thirty suitable articles were identified relating to nasopharyngeal carcinoma, oral cavity, oropharyngeal and laryngeal squamous cell carcinoma as well as primary salivary gland malignancies. Comprehensive methodological analysis identified poor reporting of detailed methodology, variations in collection, storage, pre-processing, RNA isolation and relative quantification including normalisation method. We recommend standardising the pre-processing, RNA isolation, normalisation and relative quantitation steps at biomarker discovery phase. Such standardisation would allow for bias minimisation and effective progression into clinical validation phases.
  PubDate: 2019-03-14
  DOI: 10.1007/s10585-019-09961-6
Cancer-associated fibroblasts: how do they contribute to metastasis'
- Abstract: Cancer-associated fibroblasts (CAFs) are activated fibroblasts in the tumor microenvironment. They are one of the most prominent cell types in the stroma and produce large amounts of extracellular matrix molecules, chemokines, cytokines and growth factors. Importantly, CAFs promote cancer progression and metastasis by multiple pathways. This, together with their genetic stability, makes them an interesting target for cancer therapy. However, CAF heterogeneity and limited knowledge about the function of the different CAF subpopulations in vivo, are currently major obstacles for identifying specific molecular targets that are of value for cancer treatment. In this review, we discuss recent major findings on CAF development and their metastasis-promoting functions, as well as open questions to be addressed in order to establish successful cancer therapies targeting CAFs.
  PubDate: 2019-03-07
  DOI: 10.1007/s10585-019-09959-0
Salvage treatment for recurrences after first resection of colorectal
liver metastases: the impact of histopathological growth patterns
- Abstract: The majority of patients recur after resection of colorectal liver metastases (CRLM). Patients with CRLM displaying a desmoplastic histopathological growth pattern (dHGP) have a better prognosis and lower probability of recurrence than patients with non-dHGP CRLM. The current study evaluates the impact of HGP type on the pattern and treatment of recurrences after first resection of CRLM. A retrospective cohort study was performed, including patients with known HGP type after complete resection of CRLM. All patients were treated between 2000 and 2015. The HGP was determined on the CRLM resected at first partial hepatectomy. The prognostic value of HGPs, in terms of survival outcome, in the current patient cohort were previously published. In total 690 patients were included, of which 492 (71%) developed recurrent disease. CRLM displaying dHGP were observed in 103 patients (21%). Amongst patients with dHGP CRLM diagnosed with recurrent disease, more liver-limited recurrences were seen (43% vs. 31%, p = 0.030), whereas patients with non-dHGP more often recurred at multiple locations (34% vs. 19%, p = 0.005). Patients with dHGP CRLM were more likely to undergo curatively intended local treatment for recurrent disease (adjusted odds ratio: 2.37; 95% confidence interval (CI) [1.46–3.84]; p < 0.001) compared to patients with non-dHGP. The present study demonstrates that liver-limited disease recurrence after complete resection of CRLM is more often seen in patients with dHGP, whereas patients with non-dHGP more frequently experience multi-organ recurrence. Recurrences in patients with dHGP at first CRLM resection are more likely to be salvageable by local treatment modalities, but no prognostic impact of HGPs after salvage therapy for recurrent disease was found.
  PubDate: 2019-03-06
  DOI: 10.1007/s10585-019-09960-7
The role of heterogeneous environment and docetaxel gradient in the
emergence of polyploid, mesenchymal and resistant prostate cancer cells
- Abstract: The ability of a population of PC3 prostate epithelial cancer cells to become resistant to docetaxel therapy and progress to a mesenchymal state remains a fundamental problem. The progression towards resistance is difficult to directly study in heterogeneous ecological environments such as tumors. In this work, we use a micro-fabricated “evolution accelerator” environment to create a complex heterogeneous yet controllable in-vitro environment with a spatially-varying drug concentration. With such a structure we observe the rapid emergence of a surprisingly large number of polyploid giant cancer cells (PGCCs) in regions of very high drug concentration, which does not occur in conventional cell culture of uniform concentration. This emergence of PGCCs in a high drug environment is due to migration of diploid epithelial cells from regions of low drug concentration, where they proliferate, to regions of high drug concentration, where they rapidly convert to PGCCs. Such a mechanism can only occur in spatially-varying rather than homogeneous environments. Further, PGCCs exhibit increased expression of the mesenchymal marker ZEB1 in the same high-drug regions where they are formed, suggesting the possible induction of an epithelial to mesenchymal transition (EMT) in these cells. This is consistent with prior work suggesting the PGCC cells are mediators of resistance in response to chemotherapeutic stress. Taken together, this work shows the key role of spatial heterogeneity and the migration of proliferative diploid cells to form PGCCs as a survival strategy for the cancer population, with implications for new therapies.
  PubDate: 2019-02-27
  DOI: 10.1007/s10585-019-09958-1
Modulation of cell adhesion and migration through regulation of the
immunoglobulin superfamily member ALCAM/CD166
- Abstract: In epithelial-derived cancers, altered regulation of cell–cell adhesion facilitates the disruption of tissue cohesion that is central to the progression to malignant disease. Although numerous intercellular adhesion molecules participate in epithelial adhesion, the immunoglobulin superfamily (IgSF) member activated leukocyte cell adhesion molecule (ALCAM), has emerged from multiple independent studies as a central contributor to tumor progression. ALCAM is an archetypal member of the IgSF with conventional organization of five Ig-like domains involved in homo- and heterotypic adhesions. Like many IgSF members, ALCAM is broadly expressed and involved in cellular adhesion across many cellular processes. While the redundancy of intercellular adhesion molecules (CAMs) could diminish the impact of any single CAM, consistent correlation between ALCAM expression and patient outcome for multiple cancers underscores its role in tumor progression. Unlike most oncogenes and tumor suppressors, ALCAM is neither mutated nor amplified or deleted. Experimental disruption of ALCAM-mediated adhesions implies that this IgSF member contributes to tumor progression through dynamic turnover of the protein at the cell surface. Since ALCAM is not frequently altered at the gene level, it appears to promote malignant behavior through regulation of its availability rather than its specific activity. These observations help explain its heterogeneous expression within malignant disease and the drastic changes in protein levels across tumor progression. To reveal how ALCAM contributes to tumor progression, we review regulation of its gene expression, alternative splicing, targeted proteolysis, binding partners, and surface shedding within the context of cancer. Studying ALCAM regulation has led to a novel understanding of the fine-tuning of cell adhesive state through the utilization of otherwise normal regulatory processes, which thereby enable tumor cell invasion and metastasis.
  PubDate: 2019-02-18
  DOI: 10.1007/s10585-019-09957-2
Proffered abstracts from the 17th Biennial Congress of the Metastasis
Research Society
- PubDate: 2019-02-16
  DOI: 10.1007/s10585-018-09952-z
Correction to: The therapeutic targeting of the FGFR1/Src/NF-κB signaling
axis inhibits pancreatic ductal adenocarcinoma stemness and oncogenicity
- Abstract: In the original publication, the affiliations of authors were published incorrectly. The corrected affiliations are given in this Correction.
  PubDate: 2019-02-01
  DOI: 10.1007/s10585-018-9949-z
Metastasis in the wild: investigating metastasis in non-laboratory animals
- Abstract: Humans are not the only species to spontaneously develop metastatic cancer as cases of metastasis have been reported in a wide range of animals, including dinosaurs. Mouse models have been an invaluable tool in experimental and clinical metastasis research, with the use of genetically-engineered mouse models that spontaneously develop metastasis or ectopic/orthotopic transplantation of tumour cells to wildtype or immunodeficient mice being responsible for many key advances in our understanding of metastasis. However, are there other species that can also be relevant models' Similarities to humans in terms of environmental exposures, life-span, genetics, histopathology and available therapeutics are all factors that can be considered when looking at species other than the laboratory mouse. This review will explore the occurrence of metastasis in multiple species from a variety of domestic, captive and free-living veterinary cases to assist in identifying potential alternative experimental and clinical research models relevant to humans.
  PubDate: 2019-02-01
  DOI: 10.1007/s10585-019-09956-3
Sema4D expression and secretion are increased by HIF-1α and inhibit
osteogenesis in bone metastases of lung cancer
- Abstract: Most lung cancer bone metastasis are characterized by osteolytic destruction and osteoblastic activity is significantly decreased, suggesting that hypoxia may play a critical role in the process, but the underlying mechanisms remain unknown. Semaphorin 4D (Sema4D) is a recently discovered osteogenic inhibitory factor that is expressed at high levels in lung cancers. Here, CoCl2-induced hypoxia significantly enhanced the inhibitory effect of lung cancer cell conditioned media on osteoblast differentiation by inducing the expression and secretion of Sema4D in a HIF-1α- but not HIF-2α-dependent manner. Moreover, HIF-1α directly regulated Sema4D expression by binding to bases 1171 to 798 in the Sema4D promoter. Furthermore, hypoxia increased Sema4D secretion by upregulating a disintegrin and metalloproteinase 17 (ADAM17) expression in lung cancer in a HIF-1α-dependent manner. In bone metastasis samples from 49 patients with lung cancer, Sema4D and ADAM17 expression significantly correlated with HIF-1α expression and strongly correlated with a poor differentiation status and osteolytic bone destruction. These results provide the first evidence that HIF-1α-induced Sema4D expression and secretion play important roles in lung cancer osteolytic bone metastasis by inhibiting osteoblast differentiation, thereby providing potential strategies for the treatment of bone metastasis via targeting osteoblasts.
  PubDate: 2019-02-01
  DOI: 10.1007/s10585-018-9951-5
Hepatic arterial infusion of irinotecan and EmboCept ® S results in high
tumor concentration of SN-38 in a rat model of colorectal liver metastases
- Abstract: Intraarterial chemotherapy for colorectal liver metastases (CRLM) can be applied alone or together with embolization particles. It remains unclear whether different types of embolization particles lead to higher intratumoral drug concentration. Herein, we quantified the concentrations of CPT-11 and its active metabolite SN-38 in plasma, liver and tumor tissue after hepatic arterial infusion (HAI) of irinotecan, with or without further application of embolization particles, in a rat model of CRLM. Animals underwent either systemic application of irinotecan, or HAI with or without the embolization particles Embocept® S and Tandem™. Four hours after treatment concentrations of CPT-11 and SN-38 were analyzed in plasma, tumor and liver samples by high-performance liquid chromatography. Additionally, DNA-damage and apoptosis were analyzed immunohistochemically. Tumor tissue concentrations of SN-38 were significantly increased after HAI with irinotecan and EmboCept® S compared to the other groups. The number of apoptotic cells was significantly higher after both HAI with irinotecan and EmboCept® S or Tandem™ loaded with irinotecan compared to the control group. HAI with irinotecan and EmboCept® S resulted in an increased SN-38 tumor concentration. Both HAI with irinotecan and EmboCept® S or Tandem™ loaded with irinotecan were highly effective with regard to apoptosis.
  PubDate: 2019-02-01
  DOI: 10.1007/s10585-019-09954-5
Pressurized intraperitoneal aerosol chemotherapy and its effect on
gastric-cancer-derived peritoneal metastases: an overview
- Abstract: This manuscript aspires to portray a review of the current literature focusing on manifest peritoneal metastasis (PM) derived from gastric cancer and its treatment options. Despite the development of chemotherapy and multimodal treatment options during the last decades, mortality remains high worldwide. After refreshing important epidemiological considerations, the molecular mechanisms currently accepted through which PM occurs are revised. Palliative chemotherapy is the only recommended treatment option for patients with PM of gastric cancer according to the National Comprehensive Cancer Network guidelines, although cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy demonstrated promising results in selected patients with regional PM and localized intraabdominal tumor spread. A novel treatment named pressurized intraperitoneal aerosol chemotherapy may have a promising future in improving overall survival with an acceptable postoperative complication rate and stabilizing quality of life during treatment. Additionally, the procedure has been proved to be safe for the patient and medical personnel and a feasible, repeatable method to deter metastatic proliferation. This overview comprehensively addresses this novel and promising treatment in the context of a scientifically and clinically challenging disease.
  PubDate: 2019-02-01
  DOI: 10.1007/s10585-019-09955-4
Frequent discordance in PD-1 and PD-L1 expression between primary breast
tumors and their matched distant metastases
- Abstract: Programmed death-1 (PD-1) is an immune checkpoint that is able to inhibit the immune system by binding to its ligand programmed death-ligand 1 (PD-L1). In many cancer types, among which breast cancer, prognostic and/or predictive values have been suggested for both PD-1 and PD-L1. Previous research has demonstrated discrepancies in PD-L1 expression between primary breast tumors and distant metastases, however data so far have been scarce. We therefore evaluated immunohistochemical expression levels of PD-1 and PD-L1 in primary breast tumors and their paired distant metastases, and evaluated prognostic values. Tissue microarrays from formalin-fixed paraffin-embedded resection specimens of primary breast cancers and their matched distant metastases were immunohistochemically stained for PD-1 and PD-L1. PD-1 was available in both primary tumor and metastasis in 82 patients, and PD-L1 in 49 patients. PD-1 was discrepant between primary tumor and metastasis in half of the patients (50%), PD-L1 on tumor cells was discrepant in 28.5%, and PD-L1 on immune cells in 40.8% of the patients. In primary tumors there was a correlation between PD-1 positivity and a higher tumor grade, and between immune PD-L1 and ER negativity. In survival analyses, a significantly better overall survival was observed for patients with PD-L1 negative primary breast tumors that developed PD-L1 positive distant metastases (HR 3.013, CI 1.201–7.561, p = 0.019). To conclude, PD-1 and tumor and immune PD-L1 seem to be discordantly expressed between primary tumors and their matched distant metastases in about one-third to a half of the breast cancer patients. Further, gained expression of PD-L1 in metastases seems to indicate better survival. This illustrates the need of reassessing PD-1 and PD-L1 expression on biopsies of distant metastases to optimize the usefulness of these biomarkers.
  PubDate: 2019-02-01
  DOI: 10.1007/s10585-018-9950-6
Meeting report: Metastasis Research Society (MRS) 17th Biennial conference
and associated Young Investigator Satellite Meeting (YISM) on cancer
metastasis
- Abstract: The Metastasis Research Society (MRS) 17th Biennial conference on metastasis was held on the 1st to the 5th of August 2018 at Princeton University, NJ, USA. The meeting was held around themes addressing notable aspects of the understanding and treatment of metastasis and metastatic disease covering basic, translational, and clinical research. Importantly, the meeting was largely supported by our patient advocate partners including Susan G. Komen for the Cure, Theresa’s Research Foundation and METAvivor. There were a total of 85 presentations from invited and selected speakers spread across the main congress and presentations from the preceding Young Investigator Satellite Meeting. Presentations are summarized in this report by session topic.
  PubDate: 2019-01-23
  DOI: 10.1007/s10585-018-09953-y
Radiotherapy in palliation of thoracic tumors: a phase I–II study
(SHARON project)
- Abstract: The main clinical goal for patients with advanced or metastatic thoracic cancer is palliation of tumor-related symptoms and improvement of quality of life. The aim of this phase I–II trial was to define the maximum tolerated dose (MTD) of a short-course of palliative radiotherapy (RT) and to evaluate its efficacy in terms of palliative response. A phase I trial was planned with escalating dose increments. Total doses ranged from 16 to 20 Gy delivered (BID) in two consecutive days. Dose limiting toxicity was defined as any acute grade ≥ 3 toxicity based on the RTOG scale. MTD was used in the phase II trial to evaluate the efficacy of this regimen using a two stage Simon’s design. Fifty-four patients were enrolled. The upper dose level of 20 Gy was defined as the MTD. In patients treated with this dose, the overall palliative response rate was 96.5% (CI 0.95: 81.3–99.9%). Complete pain relief rate was 50.0%. Median survival without symptomatic progression was 3 months. The tested short course accelerated regimen was well tolerated and effective in the palliative setting of metastatic or locally advanced chest cancer. A phase III trial is ongoing to validate this RT schedule. Trial registration: NCT03465553.
  PubDate: 2018-12-01
  DOI: 10.1007/s10585-018-9942-6
Systematic analysis of parameters predicting pathological axillary status
(ypN0 vs. ypN+) in patients with breast cancer converting from cN+ to ycN0
through primary systemic therapy (PST)
- Abstract: Optimization of axillary staging among patients converting from clinically node-positive disease to clinically node-negative disease through primary systemic therapy is needed. We aimed at developing a nomogram predicting the probability of positive axillary status after chemotherapy based on clinical/pathological parameters. Patients from study arm C of the SENTINA trial were included. Univariable/multivariable analyses were performed for 13 clinical/pathological parameters to predict a positive pathological axillary status after chemotherapy using logistic regression models. Odds ratios and 95%-confidence-intervals were reported. Model performance was assessed by leave-one-out cross-validation. Calculations were performed using the SAS Software (Version 9.4, SAS Institute Inc., Cary, NC, USA). 369 of 553 patients in Arm C were included in multivariable analysis. Stepwise backward variable selection based on a multivariable analysis resulted in a model including estrogen receptor (ER) status (odds ratio (OR) 3.916, 95% confidence interval (CI) 2.318–6.615, p < 0.001), multifocality (OR 2.106, 95% CI 1.203–3.689, p = 0.0092), lymphovascular invasion (OR 9.196, 95% CI 4.734–17.864, p < 0.001), and sonographic tumor diameter after PST (OR 1.034, 95% CI 1.010–1.059, p = 0.0051). When validated, our model demonstrated an accuracy of 70.2% using 0.5 as cut-point. An area under the curve of 0.81 was calculated. The use of individual parameters as predictors of lymph node status after chemotherapy resulted in an inferior accuracy. Our model was able to predict the probability of a positive axillary nodal status with a high accuracy. The use of individual parameters showed reduced predictive performance. Overall, tumor biology was the strongest parameter in our models.
  PubDate: 2018-12-01
  DOI: 10.1007/s10585-018-9938-2
Dietary regulation of metastasis
- Abstract: The impact of diet and associated lifestyle choices on the risk of developing cancer is well established. However, whether these parameters also affect cancer recurrence and survival is less well investigated. Virtually nothing is known about the impact of diet on the development of metastases. It is therefore significant that a study in this issue of Clinical and experimental metastasis reports that breast cancer-bearing mice fed on a diet rich in long-chain omega-3 fatty acids had a lower incidence of metastasis than control mice, which was associated with modified infiltration of immune cells into the tumors. These findings should form the basis of further pre-clinical evaluation with a view to clinical application.
  PubDate: 2018-12-01
  DOI: 10.1007/s10585-018-9948-0
Lung cancer with bone metastases in the United States: an analysis from
the Surveillance, Epidemiologic, and End Results database
- Abstract: The present study used the Surveillance, Epidemiology and End Results (SEER) database to identify demographic and prognostic characteristics of lung cancer with bone metastases in the United States from 2010 to 2014. 30,364 patients with metastatic lung cancer to bones were identified in the SEER database. Their information on the basic characteristics and the histological signatures of the cancer was extracted and analyzed. Joinpoint analysis was used to test the trends in annual percentage change (APC) of the incidence. 1-year survival rate among patients with metastatic lung cancer to bones was only 20.2%, and median survival time was about 3.0 months for those patients. Young age, female sex, race other than white and black, tumor in lobes, smaller tumor, adenocarcinoma, and surgery for primary site were associated with a significant survival benefit. APC of the incidence almost increased steadily on the whole and reached the level of statistical significance among the patients older than age 60. Although there are some signatures associated with better prognosis, the overall outcome remains very poor in patients with metastatic lung cancer to bones. In addition, the incidence of lung cancer with bone metastases is increasing in certain subgroups in the United States.
  PubDate: 2018-12-01
  DOI: 10.1007/s10585-018-9943-5
Efficacy and safety of 3D-conformal half body irradiation in patients with
multiple bone metastases
- Abstract: Half-body irradiation (HBI) represented a standard treatment for multiple painful bone metastases (BMs). However, its use has progressively reduced due to the associated toxicity rates. The aim of this paper was to evaluate HBI delivered by conformal radiotherapy (RT) technique in a large patients population with widespread BMs. HBI was delivered in 3 Gy fractions, bid, ≥ 6 h apart, on 2 consecutive days (total dose: 12 Gy) using 3-dimensional conformal RT (3D-CRT) box technique. The target included pelvic bones, lumbar-sacral vertebrae and upper third of femurs. Acute and late toxicity was scored based on RTOG and EORTC–RTOG scales, respectively. Pain was evaluated using the Pain-Drug scores and the Visual Analog Scale (VAS). One hundred and eighty patients were eligible for inclusion in this retrospective analysis. Grade 3 and 4 acute toxicity rates were 1.1% and 0.0%, respectively. Mean VAS before and after HBI was 5.3 versus 2.7, respectively (p: 0.0001). Based on VAS, 37.5% of patients showed complete pain relief (VAS: 0) while 38.1% had partial response (≥ 2-point VAS reduction). Overall, Pain and Drug Score reduction was observed in 76.3% and 50.4% of patients, respectively. 1-, 2-, and 3-year pain progression free survival was 77.0%, 63.4%, and 52.7%, respectively. Thirty patients (16.7%) underwent RT retreatment on the same site with median 15.9 months interval (range 2–126 months). HBI delivered with 3D-CRT technique is safe and effective. It provides long lasting pain control in patients with multiple BMs with negligible rates of relevant toxicity.
  PubDate: 2018-12-01
  DOI: 10.1007/s10585-018-9939-1
Long-chain omega-3 polyunsaturated fatty acids decrease mammary tumor
growth, multiorgan metastasis and enhance survival
- Abstract: Epidemiological studies show a reduced risk of breast cancer (BC) in women consuming high levels of long-chain (LC) omega-3 (ω-3) fatty acids (FAs) compared with women who consumed low levels. However, the regulatory and mechanistic roles of dietary ω-6 and LC-ω-3 FAs on tumor progression, metastasis and survival are poorly understood. Female BALB/c mice (10-week old) were pair-fed with a diet containing ω-3 or an isocaloric, isolipidic ω-6 diet for 16 weeks prior to the orthotopic implantation of 4T1 mammary tumor cells. Major outcomes studied included: mammary tumor growth, survival analysis, and metastases analyses in multiple organs including pulmonary, hepatic, bone, cardiac, renal, ovarian, and contralateral MG (CMG). The dietary regulation of the tumor microenvironment was evaluated in mice autopsied on day-35 post tumor injection. In mice fed the ω-3 containing diet, there was a significant delay in tumor initiation and prolonged survival relative to the ω-6 diet-fed group. The tumor size on day 35 post tumor injection in the ω-3 group was 50% smaller and the frequencies of pulmonary and bone metastases were significantly lower relative to the ω-6 group. Similarly, the incidence/frequencies and/or size of cardiac, renal, ovarian metastases were significantly lower in mice fed the ω-3 diet. The analyses of the tumor microenvironment showed that tumors in the ω-3 group had significantly lower numbers of proliferating tumor cells (Ki67+)/high power field (HPF), and higher numbers of apoptotic tumor cells (TUNEL+)/HPF, lower neo-vascularization (CD31+ vessels/HPF), infiltration by neutrophil elastase+ cells, and macrophages (F4/80+) relative to the tumors from the ω-6 group. Further, in tumors from the ω-3 diet-fed mice, T-cell infiltration was 102% higher resulting in a neutrophil to T-lymphocyte ratio (NLR) that was 76% lower (p < 0.05). Direct correlations were observed between NLR with tumor size and T-cell infiltration with the number of apoptotic tumor cells. qRT-PCR analysis revealed that tumor IL10 mRNA levels were significantly higher (six-fold) in the tumors from mice fed the ω-3 diet and inversely correlated with the tumor size. Our data suggest that dietary LC-ω-3FAs modulates the mammary tumor microenvironment slowing tumor growth, and reducing metastases to both common and less preferential organs resulting in prolonged survival. The surrogate analyses undertaken support a mechanism of action by dietary LC-ω-3FAs that includes, but is not limited to decreased infiltration by myeloid cells (neutrophils and macrophages), an increase in CD3+ lymphocyte infiltration and IL10 associated anti-inflammatory activity.
  PubDate: 2018-12-01
  DOI: 10.1007/s10585-018-9941-7