Molecular characterization of the tumor microenvironment in breast cancer

Abstract

Here we describe the comprehensive gene expression profiles of each cell type composing normal breast tissue and in situ and invasive breast carcinomas using serial analysis of gene expression. Based on these data, we determined that extensive gene expression changes occur in all cell types during cancer progression and that a significant fraction of altered genes encode secreted proteins and receptors. Despite the dramatic gene expression changes in all cell types, genetic alterations were detected only in cancer epithelial cells. The CXCL14 and CXCL12 chemokines overexpressed in tumor myoepithelial cells and myofibroblasts, respectively, bind to receptors on epithelial cells and enhance their proliferation, migration, and invasion. Thus, chemokines may play a role in breast tumorigenesis by acting as paracrine factors.

A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors

“…GIST-R cells overexpress the chemokine CXCL14 (121-fold), which has been demonstrated to be overexpressed by tumor myoepithelial cells in the tumor microenvironment of breast cancer (Allinen et al, 2004) and may enhance their proliferation, migration and invasion by acting as a paracrine factor. However, in GIST-R cells CXCL14 appears to act as an autocrine growth factor.…”

The extracellular matrix in breast cancer predicts prognosis through composition, splicing, and crosslinking

“…Myoepithelial cells are lost with malignant progression [16][17][18] and are believed to play an important tumor suppressive role in the healthy breast due to their ability to secrete the specialized extracellular matrix proteins of the BM [16,19]. Myoepithelial cells surrounding tumors show a shift in ECM protein secretion, losing expression of tumor-suppressive laminins and increasing expression of collagens [16,20].…”

“…Collagen III disrupts formation of dense, organized collagen I networks, resulting in softer ECM [94]. Loss of collagen III in mouse models is associated with tumor aggressiveness [94], though Col III is often observed to be overexpressed with increasing tumor grade [20,81,82,95]. Furthermore, reductions in collagen I density via TGFβ blockade likewise suggest that altering collagen network structure is a potential therapeutic target [96].…”

From sentinel cells to inflammatory culprits: cancer‐associated fibroblasts in tumour‐related inflammation

“…CAFs include several subpopulations with diverse origins, including myofibroblasts [characterized by α-smooth muscle actin (SMA) expression], reprogrammed local tissue fibroblasts, and bone marrow-derived progenitor cells [16]. While the distinct functional characteristics of the various CAF subsets are poorly defined, their role in supporting tumour growth has been established: CAFs have been found to promote tumour growth by directly stimulating tumour cell proliferation via secreted growth factors, and by enhancing angiogenesis [17][18][19]. Enhancement of tumour angiogenesis by CAFs can be mediated either directly, by secreting pro-angiogenic factors including interleukin (IL)-8/CXCL8, vascular endothelial growth factor (VEGF), and fibroblast growth factor (FGF)-2, or indirectly, by secreting extracellular matrix (ECM)-remodelling proteases, such as matrix metalloproteinase (MMP)-9, MMP-13, and MMP-14 that activate a multitude of latent soluble and insoluble factors with diverse activities [7,[20][21][22].…”