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Title: Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

Abstract

Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- 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-promotingmore » inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.« less

Authors:
 [1];  [1];  [1];  [2];  [3];  [1];  [2]
  1. Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel)
  2. (Israel)
  3. Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)
Publication Date:
OSTI Identifier:
22239685
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 437; Journal Issue: 3; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANGIOGENESIS; CARCINOMAS; CELL PROLIFERATION; FIBROBLASTS; INFLAMMATION; LEUKOCYTES; MAMMARY GLANDS; MICE; MORTALITY; SKIN

Citation Formats

Erez, Neta, E-mail: netaerez@post.tau.ac.il, Glanz, Sarah, Raz, Yael, Department of Obstetrics and Gynecology, LIS Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Avivi, Camilla, Barshack, Iris, and Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors. United States: N. p., 2013. Web. doi:10.1016/J.BBRC.2013.06.089.
Erez, Neta, E-mail: netaerez@post.tau.ac.il, Glanz, Sarah, Raz, Yael, Department of Obstetrics and Gynecology, LIS Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Avivi, Camilla, Barshack, Iris, & Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors. United States. doi:10.1016/J.BBRC.2013.06.089.
Erez, Neta, E-mail: netaerez@post.tau.ac.il, Glanz, Sarah, Raz, Yael, Department of Obstetrics and Gynecology, LIS Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Avivi, Camilla, Barshack, Iris, and Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv. Fri . "Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors". United States. doi:10.1016/J.BBRC.2013.06.089.
@article{osti_22239685,
title = {Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors},
author = {Erez, Neta, E-mail: netaerez@post.tau.ac.il and Glanz, Sarah and Raz, Yael and Department of Obstetrics and Gynecology, LIS Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv and Avivi, Camilla and Barshack, Iris and Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv},
abstractNote = {Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- 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.},
doi = {10.1016/J.BBRC.2013.06.089},
journal = {Biochemical and Biophysical Research Communications},
number = 3,
volume = 437,
place = {United States},
year = {Fri Aug 02 00:00:00 EDT 2013},
month = {Fri Aug 02 00:00:00 EDT 2013}
}
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