Development of UV-induced squamous cell carcinomas is suppressed in the absence of SPARC.
SPARC (Secreted Protein Acidic and Rich in Cysteine) is a multifunctional glycoprotein belonging to a group of matrix-associated factors that mediate cell-extracellular matrix interactions but have no structural roles. In the present study we investigated the contribution of SPARC to factors that influence the development of skin tumors in response to UV irradiation. A hairless SPARC-null mouse was developed and compared to control SKH1 hairless mice in terms of skin tumor induction and extracellular matrix changes occurring in response to UV-irradiation. Following 23 weeks of exposure to UVB totaling 14.5 J per cm(2), tumor development in the wild-type mice was severe, with an average of over 20 tumors per mouse, many of which were squamous cell carcinomas. Conversely, the SPARC-null mice were strikingly tumor-resistant, developing no squamous cell carcinomas and averaging less than one small papilloma per mouse. SPARC was undetectable immunohistochemically in skin from the non-irradiated control group yet was present in relatively high quantities in the basal and superficial areas of the tumor mass. The SPARC-null mice also exhibited a limited contact hypersensitivity response and were refractory to UV induced immune suppression. In conclusion, SPARC appears to have a crucial role in mediating tumor formation in response to UV irradiation.
Department of Biochemistry, University of Texas Health Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA.
Ronnie L
RL
Aycock
Amy C
AC
Bradshaw
E Helene
EH
Sage
Barry
B
Starcher
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D003877:Dermatitis, Contact / Q000503:physiopathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006965:Hyperplasia; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009381:Neoplasms, Radiation-Induced / Q000473:pathology / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology; D015676:Osteonectin / Q000235:genetics*; D012867:Skin / Q000473:pathology / Q000503:physiopathology; D012878:Skin Neoplasms / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000097:blood; D053773:Transforming Growth Factor beta1; D014466:Ultraviolet Rays / Q000009:adverse effects*
D016326:Extracellular Matrix Proteins; D015676:Osteonectin; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1