Cancers, Vol. 12, Pages 2083: Stromal CCL2 Signaling Promotes Mammary Tumor Fibrosis through Recruitment of Myeloid-Lineage Cells

Cancers, Vol. 12, Pages 2083: Stromal CCL2 Signaling Promotes Mammary Tumor Fibrosis through Recruitment of Myeloid-Lineage Cells Cancers doi: 10.3390/cancers12082083 Authors: Genevra Kuziel Victoria Thompson Joseph V. D’Amato Lisa M. Arendt Obesity is correlated with breast tumor desmoplasia, leading to diminished chemotherapy response and disease-free survival. Obesity causes chronic, macrophage-driven inflammation within breast tissue, initiated by chemokine ligand 2 (CCL2) signaling from adipose stromal cells. To understand how CCL2-induced inflammation alters breast tumor pathology, we transplanted oncogenically transformed human breast epithelial cells with breast stromal cells expressing CCL2 or empty vector into murine mammary glands and examined tumor formation and progression with time. As tumors developed, macrophages were rapidly recruited, followed by the emergence of cancer-associated fibroblasts (CAFs) and collagen deposition. Depletion of CD11b + myeloid lineage cells early in tumor formation reduced tumor growth, CAF numbers, and collagen deposition. CCL2 expression within developing tumors also enhanced recruitment of myeloid progenitor cells from the bone marrow into the tumor site. The myeloid progenitor cell population contained elevated numbers of fibrocytes, which exhibited platelet-derived growth factor receptor-alpha (PDGFRα)-dependent colony formation and growth in vitro. Together, these results suggest that chronic infl...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

Related Links:

In conclusion, it remains unclear if brain-specific regional and temporal changes occur in the expression of the different APP variants during AD progression. Since APP is also found in blood cells, assessing the changes in APP mRNA expression in peripheral blood cells from AD patients has been considering an alternative. However, again the quantification of APP mRNA in peripheral blood cells has generated controversial results. Brain APP protein has been analyzed in only a few studies, probably as it is difficult to interpret the complex pattern of APP variants and fragments. We previously characterized the soluabl...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
AbstractThe development of breast cancer (BC) is influenced by age, overweight, obesity, metabolic syndrome, and diabetes mellitus (DM), which are associated with hyperglycemia, glucose intolerance, insulin resistance, and oxidative stress. High glucose concentration increases a metastatic phenotype in cultured breast cancer cells, promoting cell proliferation, reactive species production (ROS), epithelial mesenchymal transition (EMT), and expression of proteolytic enzymes. Our aim was to determine whether diabetes mellitus favor BC progression in mice and its association with changes in the content of ROS and glycolytic a...
Source: Hormones and Cancer - Category: Cancer & Oncology Source Type: research
AbstractObesity is a preventable risk factor for breast cancer following menopause. Regardless of menopausal status, obese women who develop breast cancer have a worsened prognosis. Breast tissue is comprised of mammary epithelial cells organized into ducts and lobules and surrounded by adipose-rich connective tissue. Studies utilizing multiplein vivo models of obesity as well as human breast tissue have contributed to our understanding of how obesity alters mammary tissue. Localized changes in mammary epithelial cell populations, elevated secretion of adipokines and angiogenic mediators, inflammation within mammary adipos...
Source: Journal of Mammary Gland Biology and Neoplasia - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: Even if present results provide interesting insights on the still elusive mechanism(s) underlying the association between obesity and epithelial cell proliferation, possibly promoting neoplastic transformation, such relationship deserves further investigation in other independent datasets. PMID: 32198633 [PubMed - as supplied by publisher]
Source: Breast Cancer - Category: Cancer & Oncology Authors: Tags: Breast Cancer Source Type: research
Breast cancer resistance protein (BCRP) is a member of ATP-binding cassette (ABC) transporter proteins whose primary function is to efflux substrates bound to the plasma membrane. Impaired intestinal barrier functions play a major role in chronic low-grade inflammation (CLGI)–associated obesity, but the regulation of BCRP during obesity and its role in maintaining the intestinal barrier function during CLGI-associated obesity are unknown. In the present study, using several approaches, including efflux assays, immunoprecipitation, immunoblotting, immunohistochemistry, paracellular permeability assay, FACS, cytokine a...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Molecular Bases of Disease Source Type: research
This study investigates the potential of using adipose tissue laden with glitazones to act as a drug depot, increase adiponectin levels, and locally release glitazones to inhibit breast cancer cell proliferation. The breast cancer cell lines MCF-7 and MBA-MD-231, and the normal breast epithelial cell line MCF-10A were exposed to media containing a range of concentrations of recombinant adiponectin, pioglitazone, or conditioned media obtained from pioglitazone laden adipose tissue to determine the impact of the different treatments on cell proliferation. The MCF-7 cells demonstrated the greatest reduction in proliferation u...
Source: Molecular Biology Reports - Category: Molecular Biology Authors: Tags: Mol Biol Rep Source Type: research
Hoskin Many dietary flavonoids possess anti-cancer activities. Here, the effect of apple peel flavonoid fraction 4 (AF4) on the growth of triple-negative (MDA-MB-231, MDA-MB-468), estrogen receptor-positive (MCF-7), and HER2-positive (SKBR3) breast cancer cells was determined and compared with the effect of AF4 on normal mammary epithelial cells and dermal fibroblasts. AF4 inhibited breast cancer cell growth in monolayer cultures, as well as the growth of MCF-7 spheroids, without substantially affecting the viability of non-malignant cells. A sub-cytotoxic concentration of AF4 suppressed the proliferation of MDA-MB-23...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
Targeting CSC in a Most Aggressive Subtype of Breast Cancer TNBC. Adv Exp Med Biol. 2019;1152:311-334 Authors: Bao B, Prasad AS Abstract Triple negative breast cancer (TNBC) is a more aggressive subtype of breast cancer and is characteristic of the absence of the expressions of estrogen receptor, progesterone receptor, and human epithelial growth factor receptor 2 in breast tumor tissues. This subtype of breast cancer has the poorest prognosis, compared to other subtypes of breast cancer. TNBC is heterogeneous by showing several different histo-pathological and molecular subtypes with different pr...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Abstract Breast cancer incidence and metastasis in postmenopausal women are known to associate with obesity, but the molecular mechanisms behind this association are largely unknown. We investigated the effect of adipokine resistin on epithelial to mesenchymal transition (EMT) and stemness in breast cancer cells in vitro. Previous reports demonstrated that the inflammatory actions of resistin are mediated by the adenylyl cyclase-associated protein 1 (CAP1), which serves as its receptor. As a model for our study, we used MCF-7 and MDA-MB-231 breast cancer and MCF-10A breast epithelial cells. We showed that in MCF-7...
Source: Cytokine - Category: Molecular Biology Authors: Tags: Cytokine Source Type: research
Conclusions: We found a highly reliable FI network, which revealed LIFR, PIK3R1, and MMP12 as novel prognostic biomarker candidates for GBC. These findings could accelerate biomarker discovery and therapeutic development in this cancer. Introduction Gallbladder cancer (GBC), the sixth most common gastrointestinal cancer, is an uncommon but challenging disease. Its incidence has recently increased highly worldwide (1). The risk factors for GBC include sex, aging, obesity, chronic cholecystitis, and cholelithiasis (2, 3). Because of the lack of an effective early diagnostic method, the disease often is not diagnosed ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
More News: Breast Cancer | Cancer | Cancer & Oncology | Chemotherapy | Eating Disorders & Weight Management | Epithelial Cancer | Obesity | Pathology | Transplants