TY - JOUR
T1 - Cancer-associated fibroblasts and their putative role in potentiating the initiation and development of epithelial ovarian cancer
AU - Schauer, Isaiah G.
AU - Sood, Anil K.
AU - Mok, Samuel
AU - Liu, Jinsong
N1 - Funding Information:
Abbreviations: CAFs, cancer-associated fibroblasts; CLIC4, chloride intracellular channel 4;CXCR,CXCchemokinereceptor;CXCL,chemokine(CXCmotif)ligand;ECM,extracellular matrix; FAP-1α, fibroblast activation protein-1α; GRO-α, growth-regulated oncogene α; IL, interleukin; NF-κB, nuclear factor κB; OSCC, oral squamous cell carcinoma; RBPJκ, recombination binding protein Jκ; SDF-1α, stromal-derived factor 1α Address all correspondence to: Jinsong Liu, MD, PhD, Department of Pathology, Unit 0085, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030. E-mail: jliu@mdanderson.org 1This work was supported by the National Cancer Institute through a Specialized Program of Research Excellence grant in Ovarian Cancer (CA083639) and R01 grant to J.L., A.K.S., and S.M. and in part by the National Institutes of Health through the UT MD Anderson Cancer Center Support Grant (CA016672). Additional support was provided by an Ovarian Cancer Research Fund Program Developmental Grant. Received 10 December 2010; Revised 25 February 2011; Accepted 28 February 2011 Copyright © 2011 Neoplasia Press, Inc. All rights reserved 1522-8002/11/$25.00 DOI 10.1593/neo.101720
PY - 2011/5
Y1 - 2011/5
N2 - The progression of ovarian cancer, from cell transformation through invasion of normal tissue, relies on communication between tumor cells and their adjacent stromal microenvironment. Through a natural selection process, an autocrine-paracrine communication loop establishes reciprocal reinforcement of growth and migration signals. Thus, the cancer-activated stromal response is similar to an off-switch-defective form of the normal, universal response needed to survive insult or injury. It is becoming clearer within the cancer literature base that tumor stroma plays a bimodal role in cancer development: it impedes neoplastic growth in normal tissue while encouraging migration and tumor growth in a co-opted desmoplastic response during tumor progression. In this review, we discuss this reciprocal influence that ovarian cancer epithelial cells may have on ovarian stromal cell-reactive phenotype, stromal cell behavior, disrupted signaling networks, and tumor suppressor status in the stroma, within the context of cancer fibroblast studies from alternate cancer tissue settings. We focus on the exchange of secreted factors, in particular interleukin 1β and SDF-1α, between activated fibroblasts and cancer cells as a key area for future investigation and therapeutic development. A better understanding of the bidirectional reliance of early epithelial cancer cells on activated stromal cells could lead to the identification of novel diagnostic stromal markers and targets for therapy.
AB - The progression of ovarian cancer, from cell transformation through invasion of normal tissue, relies on communication between tumor cells and their adjacent stromal microenvironment. Through a natural selection process, an autocrine-paracrine communication loop establishes reciprocal reinforcement of growth and migration signals. Thus, the cancer-activated stromal response is similar to an off-switch-defective form of the normal, universal response needed to survive insult or injury. It is becoming clearer within the cancer literature base that tumor stroma plays a bimodal role in cancer development: it impedes neoplastic growth in normal tissue while encouraging migration and tumor growth in a co-opted desmoplastic response during tumor progression. In this review, we discuss this reciprocal influence that ovarian cancer epithelial cells may have on ovarian stromal cell-reactive phenotype, stromal cell behavior, disrupted signaling networks, and tumor suppressor status in the stroma, within the context of cancer fibroblast studies from alternate cancer tissue settings. We focus on the exchange of secreted factors, in particular interleukin 1β and SDF-1α, between activated fibroblasts and cancer cells as a key area for future investigation and therapeutic development. A better understanding of the bidirectional reliance of early epithelial cancer cells on activated stromal cells could lead to the identification of novel diagnostic stromal markers and targets for therapy.
UR - http://www.scopus.com/inward/record.url?scp=79955870488&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955870488&partnerID=8YFLogxK
U2 - 10.1593/neo.101720
DO - 10.1593/neo.101720
M3 - Review article
C2 - 21532880
AN - SCOPUS:79955870488
SN - 1522-8002
VL - 13
SP - 393
EP - 405
JO - Neoplasia
JF - Neoplasia
IS - 5
ER -