Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2008;6(3-4):155-63.
doi: 10.1089/lrb.2008.1011.

Roles of integrins in tumor angiogenesis and lymphangiogenesis

Barbara Garmy-Susini  1 , Judith A Varner
Affiliations
Review

Roles of integrins in tumor angiogenesis and lymphangiogenesis

Barbara Garmy-Susini et al. Lymphat Res Biol. 2008.

Abstract

The lifelong dedication of Dr. Judah Folkman to understand how tumors co-opt vasculature to promote tumor growth and spread resulted in the development of an astounding body of knowledge and development of new clinical therapeutics for cancer. Angiogenesis is a critical point in the development and dissemination of most human tumors. Tumor-associated lymphangiogenesis also plays an important role in mediating tumor spread to lymph nodes. The molecular regulations of these processes are complex, and many key molecular families have been implicated in the regulation of angiogenesis and lymphangiogenesis. By regulating cell-cell and cell-matrix contacts, integrins participate in blood and lymphatic vessel growth by promoting endothelial cell migration and survival. Understanding the underlying mechanisms by which integrins promote tumor-associated blood and lymphatic vessel development might provide important modalities for the therapeutic intervention of metastatic spread. This review focuses on the role of integrins in angiogenesis and lymphangiogenesis. Integrins represent potential targets for pharmacological agents and open new avenues for the control of metastatic spread in the treatment of malignancies. This article is dedicated to the memory of Dr. Judah Folkman, an amazing and caring teacher, scientist, physician, and friend.

PubMed Disclaimer

Figures

FIG. 1
FIG. 1
Mechanisms regulating angiogenesis and lymphangiogenesis. Tumor cells near pre-existing blood vessels secrete growth factors and chemokines such as VEGF-A, bFGF, and TNFα that stimulate quiescent vascular endothelium to enter the cell cycle. Tumors also secrete factors such as VEGF-C, VEGFD, or VEGF-A that stimulate the growth of new lymphatic vessels in the peritumoral space. These growth factors activate or upregulate expression of integrins such as α1β1, α2β1, α4β1, α5β1, and αvβ3 on blood vessels and α4β1, α9β1, and α1β1 on lymphatic vessels. Tumor derived VEGF-C also promotes new lymphatic vessel growth in draining lymph nodes. These integrins then promote endothelial cell migration and survival during invasion of tumor tissue, resulting in the creation of new vessels sprouts. The new blood vessels promote tumor growth by removing waste products and providing nutrients. These new blood and lymphatic vessels also provide an avenue for tumor metastasis. Lymphangiogenesis promotes metastasis to lymph nodes and, sometimes, more distant tissues such as lung, whereas angiogenesis promotes metastasis to local and distant sites, such as lung.
FIG. 2
FIG. 2
Integrin family of adhesion receptors. Each integrin receptor heterodimer binds a specific set of endogenous ligands, which may include ligands in the ECM, soluble ligands, and ligands on other cell surfaces. Integrins are divalent cation-dependent heterodimeric membrane glycoproteins comprised of noncovalently associated α and β subunits. Each integrin subunit consists of an extracellular domain, a single transmembrane region, and a short (approximately 30 to 40 amino acids) cytoplasmic region. Upon ligand binding, a series of intracellular signaling events is initiated. These pathways are associated with enhanced cell proliferation, migration, and survival.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Carmeliet P. Angiogenesis in life, disease and medicine. Nature. 2005;438:932–936. - PubMed
    1. Dang DT, Chun SY, Burkitt K, Abe M, Chen S, Havre P, Mabjeesh NJ, Heath EI, Vogelzang NJ, Cruz–Correa M, Blayney DW, Ensminger WD, St Croix B, Dang NH, Dang LH. Hypoxia-inducible factor-1 target genes as indicators of tumor vessel response to vascular endothelial growth factor inhibition. Cancer Res. 2008;68:1872–1880. - PubMed
    1. Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003;3:721–732. - PubMed
    1. Klagsbrun M. Mediators of angiogenesis: The biological significance of basic fibroblast growth factor (bFGF)-heparin and heparan sulfate interactions. Semin Cancer Biol. 1992;3:81–87. - PubMed
    1. Chen JX, Chen Y, DeBusk L, Lin W, Lin PC. Dual functional roles of Tie-2/angiopoietin in TNF-alpha-mediated angiogenesis. Am J Physiol Heart Circ Physiol. 2004;287:H187–195. - PubMed

Publication types

LinkOut - more resources