A naturally occurring truncated beta3 integrin in tumor cells: native anti-integrin involved in tumor cell motility.
Alternatively spliced integrins may play an important role in integrin mediated tumor cell adhesion, spreading, and migration. Here we report in human tumor cells a naturally occurring alternatively spliced variant of the beta3 integrin [i.e., truncated (tr) beta3] that lacked a cytoplasmic and a transmembrane domain. The presence of trbeta3 was demonstrated at the mRNA level by RT-PCR, cloning, and sequencing; at the protein level by immunohistochemistry and Western Blotting. The alternately spliced beta3 integrin was detected in human prostate carcinomas, breast carcinomas, and melanoma cells. Expression in vivo was confirmed by immunohistochemistry with an antibody to trbeta3 that does not recognize wild type beta3. Tumor cells secreted this protein and deposited it on the extracellular matrix. Secreted trbeta3 inhibited adhesion of melanoma and prostate cancer cells to fibronectin and vitronectin, which was partially reversed by adsorption of trbeta3 from the media. Confocal microscopy and time lapse live cell microscopy demonstrated that trbeta3 distributed to the trailing edge of migrating cells, which may represent an alternative cell detachment mechanism in these cells. Results suggest that trbeta3 may act as an anti-integrin and play a crucial role in cell migration, which is an important process in tumor invasion and metastasis.
Jin
Rongxian
R
Department of Radiation Oncology, Wayne State University, Detroit, Michigan 48202, USA.
Trikha
Mohit
M
Cai
Yinlong
Y
Grignon
David
D
Honn
Kenneth V
KV
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D017434:Protein Structure, Tertiary / Q000235:genetics; D014158:Transcription, Genetic; D019096:Vitronectin / Q000378:metabolism
D005353:Fibronectins; D039661:Integrin beta3; D019096:Vitronectin