Abstract
BackgroundTetraspanins are transmembrane proteins that serve as scaffolds for multiprotein complexes containing, for example, integrins, growth factor receptors and matrix metalloproteases, and modify their functions in cell adhesion, migration and transmembrane signaling. CD151 is part of the tetraspanin family and it forms tight complexes with β1 and β4 integrins, both of which have been shown to be required for tumorigenesis and/or metastasis in transgenic mouse models of breast cancer. High levels of the tetraspanin CD151 have been linked to poor patient outcome in several human cancers including breast cancer. In addition, CD151 has been implicated as a promoter of tumor angiogenesis and metastasis in various model systems.MethodsHere we investigated the effect of Cd151 deletion on mammary tumorigenesis by crossing Cd151-deficient mice with a spontaneously metastasising transgenic model of breast cancer induced by the polyoma middle T antigen (PyMT) driven by the murine mammary tumor virus promoter (MMTV).ResultsCd151 deletion did not affect the normal development and differentiation of the mammary gland. While there was a trend towards delayed tumor onset in Cd151−/− PyMT mice compared to Cd151+/+ PyMT littermate controls, this result was only approaching significance (Log-rank test P-value =0.0536). Interestingly, Cd151 deletion resulted in significantly reduced numbers and size of primary tumors but did not appear to affect the number or size of metastases in the MMTV/PyMT mice. Intriguingly, no differences in the expression of markers of cell proliferation, apoptosis and blood vessel density was observed in the primary tumors.ConclusionThe findings from this study provide additional evidence that CD151 acts to enhance tumor formation initiated by a range of oncogenes and strongly support its relevance as a potential therapeutic target to delay breast cancer progression.
Highlights
Tetraspanins are transmembrane proteins that serve as scaffolds for multiprotein complexes containing, for example, integrins, growth factor receptors and matrix metalloproteases, and modify their functions in cell adhesion, migration and transmembrane signaling
In order to address this question, we studied the effect of Cd151 deletion on de novo breast tumorigenesis and spontaneous metastasis in the very well characterized mammary tumor virus promoter (MMTV)/polyoma middle T antigen (PyMT) transgenic breast cancer mouse model [16]
Loss of Cd151 significantly decreases mammary tumor multiplicity and growth To avoid the kidney phenotype that has been described in FVB/ N (FVB) Cd151−/− mice [21], we chose to investigate the effects of Cd151 deletion on mammary tumorigenesis on a F1 (FVB×B6) background
Summary
Tetraspanins are transmembrane proteins that serve as scaffolds for multiprotein complexes containing, for example, integrins, growth factor receptors and matrix metalloproteases, and modify their functions in cell adhesion, migration and transmembrane signaling. CD151 is part of the tetraspanin family and it forms tight complexes with β1 and β4 integrins, both of which have been shown to be required for tumorigenesis and/or metastasis in transgenic mouse models of breast cancer. The tetraspanin CD151 is part of the tetraspanin family of transmembrane proteins, which consists of 33 members in humans These proteins serve as scaffolds for multiprotein complexes (called TEMs or Tetraspanin-Enriched Microdomains) where they associate with molecules such as integrins, growth factor receptors and matrix metalloproteases, modifying their functions in various cellular processes. In accordance with its association with poor prognostic in patients, CD151 has been implicated as a promoter of tumor angiogenesis and/or metastasis in vitro in human breast cancer cell lines and in several in vivo model systems including xenografts [5,11], matrigel plug and tumor implantation experiments [12], as well as experimental metastasis models [13,14]. A recent study showed that CD151 plays a role in mammary cell proliferation, suggesting the involvement of CD151 in tumor cell growth [15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
