Characterization of heterotypic interaction effects in vitro to deconvolute global gene expression profiles in cancer

Abstract

Background: Perturbations in cell-cell interactions are a key feature of cancer. However, little is known about the systematic effects of cell-cell interaction on global gene expression in cancer.

Tumor STAT1 Transcription Factor Activity Enhances Breast Tumor Growth and Immune Suppression Mediated by Myeloid-derived Suppressor Cells

“…Previous work by the Brown group had demonstrated increased tumor STAT1 immunostaining, especially at the tumor-stromal borders, in human breast tumor specimens as compared with normal breast tissue (30). We sought to validate and extend these findings in human biopsy samples scored as either DCIS or as invasive carcinoma.…”

GATA3 inhibits breast cancer growth and pulmonary breast cancer metastasis

“…Interestingly, the 30 most differentially regulated genes (Supplementary Tables 1 and 2) included several genes related to breast cancer metastasis and malignancy (Goodison et al, 2005;Minn et al, 2005;Buess et al, 2007;Gupta et al, 2007b;Hautala et al, 2008). The genes upregulated in GATA3-overexpressing cells included inhibitors of breast cancer growth and metastasis, such as PAEP (progestagenassociated endometrial protein) (Glycodelin) and DLC1 (deleted in liver cancer 1), whereas the prometastatic genes, ID1, ID3, LY6E, KRTHB1 and RARRES3, as well as the interferon-response genes, MX1, OAS1, G1P3 and IFI44L, were found to be downregulated in the presence of high GATA3 expression.…”

Origin of carcinoma associated fibroblasts

“…Yet, spontaneous cross talk between epithelial and stromal cells induces the expression of genes in both the stroma and cancer cells. [63][64][65][66][67][68][69][70][71] These genes include classical cancer stroma markers that reportedly may promote oncogenic potential of adjacent epithelia. 2,3,[72][73][74] This is possibly due to the late presentation with carcinoma disease in human life span.…”

“…[115][116][117][118] The fibroblast response is hardwired in the genome as part of the cancer's resemblance to a chronic wound, aiming at support of epithelial cell survival and expansion. [119][120][121][122][123][124][125][126][127][128] In addition to parsimony, this hypothesis offers clear predictions to scientifically test against corresponding null hypotheses; (1) That co-culture of cancer cells with normal fibroblasts will induce expression of CAF-specific genes in the fibroblasts, [63][64][65][66][67][68][69][70][71] [63][64][65][66][67][68][69][70][71] Many of the genes shown to be activated in these co-cultures are known markers of CAFs in vivo, such as MMP1, MMP3, collagens, TNC, etc. Evidence that this reciprocal interaction promotes cancer includes the anti-cancer effect of Imatinib, on carcinoma animal models.…”