The role of CXC chemokines in the regulation of angiogenesis in non-small cell lung cancer.
Angiogenesis is a critical component of tumor biology. In recent years newer techniques of cell and molecular biology have led to important advances in our understanding of this process. The regulation of angiogenesis depends on a balance between the activity of local factors that promote (angiogenic factors) or inhibit (angiostatic factors) neovascularization. Nowhere is this paradigm of a balance more apparent than in the study of tumor-associated angiogenesis. Tumors promote angiogenesis through a combination of overexpression of angiogenic factors and local inhibition of angiostatic factors. This strategy leads to an angiogenic environment that promotes tumor growth and metastases. Our laboratory has focused studies on the role of the CXC chemokine family in the regulation of angiogenesis by non-small cell lung cancer (NSCLC). In this article, we review our findings that the CXC chemokine family is composed of members that are either angiogenic or angiostatic. We have found that in NSCLC an imbalance exists in the expression of these factors that favors tumor-derived angiogenesis, and therefore tumor growth and metastases. Furthermore, when this imbalance is corrected to reduce the presence of angiogenic factors or increase the presence of angiostatic factors, tumor growth and metastases are reduced.
Arenberg
D A
DA
Department of Internal Medicine, The University of Michigan Medical School, Ann Arbor 48109-0360, USA.
Polverini
P J
PJ
Kunkel
S L
SL
Shanafelt
A
A
Hesselgesser
J
J
Horuk
R
R
Strieter
R M
RM
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply*; D002455:Cell Division / Q000502:physiology; D019743:Chemokines, CXC / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000473:pathology*
D019743:Chemokines, CXC