Induction of type XVI collagen expression facilitates proliferation of oral cancer cells.
Type XVI collagen belongs to the family of fibril-associated collagens with interrupted triple helices (FACIT). Recently, high affinity to integrin alpha1beta1 has been shown allowing cells expressing those integrins to attach and spread on recombinant type XVI collagen. Here, we show that type XVI collagen is overexpressed in dysplastic areas of mucosal epithelium from oral squamous cell carcinoma (OSCC) patients. Induction of its expression in OSCC cell lines (COLXVI cells) leads to an increased expression of Kindlin-1. Moreover, we demonstrate a significantly increased Kindlin-1/beta1-integrin interaction. Additionally, we detected a higher number of activated beta1-integrins in COLXVI cells and found a neo-expression of alpha1 integrin subunit on these cells. FACS analysis revealed a significantly higher amount of COLXVI cells in S-phase and G2/M-phase 6h after synchronisation leading to a markedly higher proliferation activity. Blocking beta1-integrins with a specific antibody resulted in reduced proliferation of COLXVI cells. In summary, we demonstrate that overexpression of type XVI collagen in aberrant oral keratinocytes leads to Kindlin-1 induction, increased Kindlin-1/beta1-integrin interaction, integrin activation and subsequently to a proliferative cellular phenotype.
Centre for Medical Biotechnology, Regensburg, Germany.
Sabine
S
Ratzinger
Susanne
S
Grässel
Albert
A
Dowejko
Torsten E
TE
Reichert
Richard J
RJ
Bauer
D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D039423:Integrin alpha1 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D016196:S Phase / Q000502:physiology; D014162:Transfection
C481130:COL16A1 protein, human; C475301:FERMT1 protein, human; C477322:FERMT3 protein, human; D039423:Integrin alpha1; D019012:Integrin beta1; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D003094:Collagen