Collagen XVII promotes integrin-mediated squamous cell carcinoma transmigration--a novel role for alphaIIb integrin and tirofiban.
The expression of collagen XVII (BP180), a transmembrane hemidesmosomal component, is upregulated in invasive areas of epithelial tumors. The collagenous ectodomain of collagen XVII is cleaved from the plasma membrane of keratinocytes and malignant epithelial cells. The released ectodomain is predicted to regulate cell detachment, differentiation, and motility. We report that the cell adhesion domain of collagen XVII, Col15, is able to chemotactically attract invasive HSC-3 SCC cells but not keratinocytes. Analysis of integrin expression revealed that HSC-3 cells, unlike keratinocytes, express alphaIIb integrin, a platelet-specific fibrinogen receptor. We show that this novel chemotactic function is mediated by the known Col15-binding integrins alpha5beta1 and alphav and the platelet integrin alphaIIb. Moreover, we report that tirofiban, a FDA-proved alphaIIb integrin-blocking drug widely used for the therapy of acute coronary ischaemic syndrome and the prevention of thrombotic complications, inhibits the Col15 chemotaxis of HSC-3 carcinoma cells. Together, these data demonstrate a novel interaction between collagen XVII and alphaIIb integrin and also suggest a possibility to use tirofiban to inhibit the invasion and progression of alphaIIb expressing SCC tumors.
Department of Diagnostic and Oral Medicine, University of Oulu, and Oulu University Hospital, Oulu, Finland.
M
M
Parikka
L
L
Nissinen
T
T
Kainulainen
L
L
Bruckner-Tuderman
T
T
Salo
J
J
Heino
K
K
Tasanen
D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001324:Autoantigens / Q000737:chemistry / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000503:physiopathology / Q000517:prevention & control; D024041:Non-Fibrillar Collagens / Q000737:chemistry / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014945:Wound Healing / Q000502:physiology; D000097794:Kalinin; D000097805:Collagen Type XVII
D000970:Antineoplastic Agents; D001324:Autoantigens; D015815:Cell Adhesion Molecules; D039081:Integrin alpha5beta1; D024041:Non-Fibrillar Collagens; D010975:Platelet Aggregation Inhibitors; D040201:Platelet Membrane Glycoprotein IIb; D000077466:Tirofiban; D014443:Tyrosine; D000097794:Kalinin; D000097805:Collagen Type XVII