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Int J Clin Exp Pathol 2012;5(9):863-873

Review Article
Hematopoietic stem cell derived carcinoma-associated fibroblasts: a novel origin

Lindsay T McDonald, Amanda C LaRue

The Department of Pathology and Laboratory Medicine and Hollings Cancer Center, Medical University of South Carolina, and 3Research
Services, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA.

Received August 2, 2012; Accepted September 23, 2012; Epub October 20, 2012; Published October 30, 2012

Abstract: Researchers have begun to appreciate the significant role that the microenvironment plays in tumorigenesis and are now shedding
light on the role of the stroma in induction and progression of solid tumors. While the stroma of solid tumors is comprised of many cell types,
including vascular and immune cells, one of the most prominent cell types in the tumor stroma is the fibroblast, called the
carcinoma-associated fibroblast (CAF) or tumor-associated fibroblast (TAF). The interaction between CAFs and tumor cells is quite complex.
CAFs have been implicated in tumor angiogenesis, immunosuppression, tumor cell proliferation and aggressiveness, genetic instability, and
metastasis. However, their specific roles in each of these processes have only been partially elucidated. Determining the role of CAFs has
been complicated by the fact that researchers have demonstrated heterogeneity in the stromal fibroblast population. This heterogeneity has
brought about the concept of multiple origins for CAFs. While many origins of CAFs have been suggested, in our own laboratory we have
identified a novel hematopoietic stem cell (HSC) origin of CAFs. Given the profound role of CAFs in tumor progression and prognosis, the CAF
represents an exciting potential therapeutic target. The heterogeneity of the CAF population makes research directed at investigating the roles
and origins of CAFs critical to development of such anti-tumor therapies. (IJCEP1208002).

Keywords: Hematopoietic stem cells, carcinoma associated fibroblasts, tumor associated fibroblasts, stem cell plasticity, tumor progression,

Address all correspondence to:
Dr. Amanda C LaRue
Research Services, Ralph H. Johnson Veterans
Affairs Medical Center, 109 Bee Street
Charleston SC, 29403, USA.
E-mail: laruerc@musc.edu