TY - JOUR
T1 - Semaphorin signaling in cancer cells and in cells of the tumor microenvironment - Two sides of a coin
AU - Capparuccia, Lorena
AU - Tamagnone, Luca
PY - 2009
Y1 - 2009
N2 - Semaphorins are a large family of secreted and membrane-bound molecules that were initially implicated in the development of the nervous system and in axon guidance. More recently, they have been found to regulate cell adhesion and motility, angiogenesis, immune responses, and tumor progression. Semaphorin receptors, the neuropilins and the plexins, are expressed by a wide variety of cell types, including endothelial cells, bone-marrow-derived cells and cancer cells. Interestingly, a growing body of evidence indicates that semaphorins also have an important role in cancer. It is now known that cancer progression, invasion and metastasis involve not only genetic changes in the tumor cells but also crosstalk between tumor cells and their surrounding non-tumor cells. Through the recruitment of endothelial cells, leukocytes, pericytes and fibroblasts, and the local release of growth factors and cytokines, the tumor microenvironment can mediate tumorcell survival, tumor proliferation and regulation of the immune response. Moreover, by conferring cancer cells with an enhanced ability to migrate and invade adjacent tissues, extracellular regulatory signals can play a major role in the metastatic process. In this Commentary, we focus on the emerging role of semaphorins in mediating the crosstalk between tumor cells and multiple stromal cell types in the surrounding microenvironment.
AB - Semaphorins are a large family of secreted and membrane-bound molecules that were initially implicated in the development of the nervous system and in axon guidance. More recently, they have been found to regulate cell adhesion and motility, angiogenesis, immune responses, and tumor progression. Semaphorin receptors, the neuropilins and the plexins, are expressed by a wide variety of cell types, including endothelial cells, bone-marrow-derived cells and cancer cells. Interestingly, a growing body of evidence indicates that semaphorins also have an important role in cancer. It is now known that cancer progression, invasion and metastasis involve not only genetic changes in the tumor cells but also crosstalk between tumor cells and their surrounding non-tumor cells. Through the recruitment of endothelial cells, leukocytes, pericytes and fibroblasts, and the local release of growth factors and cytokines, the tumor microenvironment can mediate tumorcell survival, tumor proliferation and regulation of the immune response. Moreover, by conferring cancer cells with an enhanced ability to migrate and invade adjacent tissues, extracellular regulatory signals can play a major role in the metastatic process. In this Commentary, we focus on the emerging role of semaphorins in mediating the crosstalk between tumor cells and multiple stromal cell types in the surrounding microenvironment.
KW - Cell Biology
KW - Plexins
KW - Semaphorins
KW - Tumor
KW - Tumor microenvironment
KW - Cell Biology
KW - Plexins
KW - Semaphorins
KW - Tumor
KW - Tumor microenvironment
UR - http://hdl.handle.net/10807/140835
UR - http://jcs.biologists.org/cgi/reprint/122/11/1723
U2 - 10.1242/jcs.030197
DO - 10.1242/jcs.030197
M3 - Article
SN - 0021-9533
VL - 122
SP - 1723
EP - 1736
JO - Journal of Cell Science
JF - Journal of Cell Science
ER -