TY - JOUR
T1 - Stromal fibroblasts in digestive cancer
AU - Worthley, Daniel L.
AU - Giraud, Andrew S.
AU - Wang, Timothy C.
N1 - Funding Information:
Sources of support: The Royal Australasian College of Physicians Cottrell Fellowship (D.L.W.) and the Queensland State Government, Smart State PhD award (D.L.W).
PY - 2010/12
Y1 - 2010/12
N2 - The normal gastrointestinal stroma consists of extra-cellular matrix and a community of stromal cells including fibroblasts, myofibroblasts, smooth muscle cells, pericytes, endothelium and inflammatory cells. α-smooth muscle actin (α-SMA) positive stromal fibroblasts, often referred to as myofibroblasts or activated fibroblasts, are critical in the development of digestive cancer and help to create an environment that is permissive of tumor growth, angiogenesis and invasion. This review focusses on the contribution of activated fibroblasts in carcinogenesis and where possible directly applies this to, and draws on examples from, gastrointestinal cancer. In particular, the review expands on the definition, types and origins of activated fibroblasts. It examines the molecular biology of stromal fibroblasts and their contribution to the peritumoral microenvironment and concludes by exploring some of the potential clinical applications of this exciting branch of cancer research. Understanding the origin and biology of activated fibroblasts will help in the development of an integrated epithelial-stromal sequence to cancer that will ultimately inform cancer pathogenesis, natural history and future therapeutics.
AB - The normal gastrointestinal stroma consists of extra-cellular matrix and a community of stromal cells including fibroblasts, myofibroblasts, smooth muscle cells, pericytes, endothelium and inflammatory cells. α-smooth muscle actin (α-SMA) positive stromal fibroblasts, often referred to as myofibroblasts or activated fibroblasts, are critical in the development of digestive cancer and help to create an environment that is permissive of tumor growth, angiogenesis and invasion. This review focusses on the contribution of activated fibroblasts in carcinogenesis and where possible directly applies this to, and draws on examples from, gastrointestinal cancer. In particular, the review expands on the definition, types and origins of activated fibroblasts. It examines the molecular biology of stromal fibroblasts and their contribution to the peritumoral microenvironment and concludes by exploring some of the potential clinical applications of this exciting branch of cancer research. Understanding the origin and biology of activated fibroblasts will help in the development of an integrated epithelial-stromal sequence to cancer that will ultimately inform cancer pathogenesis, natural history and future therapeutics.
KW - Bone-marrow derived cells
KW - Cancer stroma
KW - Digestive system neoplasms
KW - Fibroblasts
KW - Neoplasms
UR - http://www.scopus.com/inward/record.url?scp=78649637521&partnerID=8YFLogxK
U2 - 10.1007/s12307-009-0033-8
DO - 10.1007/s12307-009-0033-8
M3 - Article
C2 - 21209778
AN - SCOPUS:78649637521
SN - 1875-2292
VL - 3
SP - 117
EP - 125
JO - Cancer Microenvironment
JF - Cancer Microenvironment
IS - 1
ER -