Tumor cell alpha3beta1 integrin and vascular laminin-5 mediate pulmonary arrest and metastasis.
Arrest of circulating tumor cells in distant organs is required for hematogenous metastasis, but the tumor cell surface molecules responsible have not been identified. Here, we show that the tumor cell alpha3beta1 integrin makes an important contribution to arrest in the lung and to early colony formation. These analyses indicated that pulmonary arrest does not occur merely due to size restriction, and raised the question of how the tumor cell alpha3beta1 integrin contacts its best-defined ligand, laminin (LN)-5, a basement membrane (BM) component. Further analyses revealed that LN-5 is available to the tumor cell in preexisting patches of exposed BM in the pulmonary vasculature. The early arrest of tumor cells in the pulmonary vasculature through interaction of alpha3beta1 integrin with LN-5 in exposed BM provides both a molecular and a structural basis for cell arrest during pulmonary metastasis.
Wang
Hui
H
Dept. of Pathology, Rm. 916D ARC, Children's Hospital of Philadelphia, 3615 Civic Center Blvd., Philadelphia, PA 19104, USA.
Fu
Weili
W
Im
Jae Hong
JH
Zhou
Zengyi
Z
Santoro
Samuel A
SA
Iyer
Vandana
V
DiPersio
C Mike
CM
Yu
Qian-Chun
QC
Quaranta
Vito
V
Al-Mehdi
Abu
A
Muschel
Ruth J
RJ
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001485:Basement Membrane / Q000378:metabolism / Q000648:ultrastructure; D001808:Blood Vessels / Q000033:anatomy & histology / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D039422:Integrin alpha3 / Q000276:immunology / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism*; D008024:Ligands; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism*; D051381:Rats; D000097794:Kalinin
D000906:Antibodies; D015815:Cell Adhesion Molecules; D039422:Integrin alpha3; D019012:Integrin beta1; D008024:Ligands; D000097794:Kalinin