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Published on: September 16, 2019
A naturally occurring truncated beta3 integrin in tumor cells: native anti-integrin involved in tumor cell motility
Rongxian Jin1, Mohit Trikha, Yinlong Cai
1Department of Radiation Oncology, Wayne State University, Detroit, Michigan 48202, USA.
Abstract:
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.
Insights
A novel truncated beta3 integrin (trbeta3) variant was identified in human tumors. This secreted protein inhibits cancer cell adhesion and may play a role in tumor cell migration and metastasis.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Integrins are crucial for cell adhesion, migration, and signaling.
- Alternative splicing of integrins can generate variants with altered functions.
- Tumor cell migration and metastasis are complex processes involving integrin dynamics.
Purpose of the Study:
- To identify and characterize alternatively spliced integrin variants in human tumors.
- To investigate the functional role of a novel truncated beta3 integrin (trbeta3) variant.
- To explore the potential involvement of trbeta3 in tumor cell adhesion and migration.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR), cloning, and sequencing for mRNA detection.
- Immunohistochemistry and Western Blotting for protein level analysis.
- Cell adhesion assays, confocal microscopy, and live cell time-lapse microscopy.
Main Results:
- A naturally occurring truncated beta3 integrin (trbeta3) variant, lacking cytoplasmic and transmembrane domains, was identified in human prostate carcinomas, breast carcinomas, and melanoma cells.
- Tumor cells secreted trbeta3, which was deposited on the extracellular matrix.
- Secreted trbeta3 inhibited cancer cell adhesion to fibronectin and vitronectin and localized to the trailing edge of migrating cells.
Conclusions:
- The truncated beta3 integrin (trbeta3) functions as an anti-integrin.
- trbeta3 may play a significant role in regulating cancer cell migration, potentially impacting tumor invasion and metastasis.
- This finding highlights the importance of alternatively spliced integrins in cancer biology.
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