Antiintegrin alpha v beta 3 blocks human breast cancer growth and angiogenesis in human skin.
Angiogenesis plays a fundamental role in human breast tumor progression. In fact, recent findings indicate that vascular density is a prognostic indicator of breast cancer disease status. Evidence is presented that the integrin alpha v beta 3 is not only a marker of human breast tumor-associated blood vessels, but that it plays a significant role in human angiogenesis and breast tumor growth. To assess the role of alpha v beta 3-dependent angiogenesis in the progression of human breast cancer, we examined a SCID mouse/human chimeric model with transplanted full thickness human skin containing alpha v beta 3-negative human breast tumor cells. This tumor induced a human angiogenic response as measured by vascular cell immunoreactivity with monoclonal antibodies LM609 and P2B1 directed to human alpha v beta 3 and CD31, respectively. Intravenous administration of LM609 either prevented tumor growth or markedly reduced tumor cell proliferation within the microenvironment of the human skin. These LM609-treated tumors not only contained significantly fewer human blood vessels but also appeared considerably less invasive than tumors in control animals. These findings demonstrate that alpha v beta 3 antagonists may provide an effective antiangiogenic approach for the treatment of human breast cancer.
Brooks
P C
PC
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Strömblad
S
S
Klemke
R
R
Visscher
D
D
Sarkar
F H
FH
Cheresh
D A
DA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors* / Q000502:physiology; D012867:Skin / Q000098:blood supply
D000911:Antibodies, Monoclonal; D019030:Receptors, Vitronectin