title: Cancer associated fibroblasts express pro-inflammatory factors in human breast and ovarian tumors.
abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.
authors.affiliation: Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978, Israel. netaerez@post.tau.ac.il
authors.forename: Neta
authors.initials: N
authors.lastname: Erez
authors.forename: Sarah
authors.initials: S
authors.lastname: Glanz
authors.forename: Yael
authors.initials: Y
authors.lastname: Raz
authors.forename: Camilla
authors.initials: C
authors.lastname: Avivi
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism / Q000473:pathology; D054360:Chemokine CXCL1 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D018450:Disease Progression; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis; D016328:NF-kappa B / Q000096:biosynthesis; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012189:Retrospective Studies; D015398:Signal Transduction / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016328:NF-kappa B; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: Breast cancer; CAFs; Inflammation; Ovarian cancer; Tumor microenvironment