Amphiregulin overexpression results in rapidly growing keratinocytic tumors: an in vivo xenograft model of keratoacanthoma.
Keratoacanthoma (KA) is a variant of cutaneous squamous cell carcinoma (SCC) known for rapid growth and potential for involution. Little is known about the basis for the rapid growth because of the dearth of model systems. We hypothesized that amphiregulin (AR), a keratinocyte autocrine growth factor, had a significant role. Using immunohistochemistry, we compared 21 KA, 6 conventional SCC, and 6 basal cell carcinomas (BCC) for AR expression. All KA were positive for AR, the majority with strong immunoreactivity. The SCC were positive (5 of 6), with generally weak staining; no BCC were positive. We developed laboratory model systems to study AR overexpression in keratinocytes and its role in the pathogenesis of KA. A retroviral transduction strategy was used to overexpress AR in the HaCaT keratinocyte-like cell line. The AR overexpressing cells (HaCaT-AR) displayed autonomous proliferation in serum-free media when compared with controls (HaCaT-NIE). To develop an in vivo model, xenografts of HaCaT-AR and HaCaT-NIE were grown on SCID mice. The HaCaT-NIE cells formed thin tumors resembling conventional SCC. The HaCaT-AR cells formed rapidly growing tumors with AR expression similar to KA. HaCaT-AR cells may represent a new system for the further evaluation of KA.
Billings
Steven D
SD
Departments of Pathology and Laboratory Medicine and Dermatology, Indiana University School Of Medicine, Indianapolis, Indiana 46202, USA. sdbillin@iupin.edu
Southall
Michael D
MD
Li
Tao
T
Cook
Paul W
PW
Baldridge
LeeAnn
L
Moores
William B
WB
Spandau
Daniel F
DF
Foley
John G
JG
Travers
Jeffrey B
JB
D066258:Amphiregulin; D000818:Animals; D002280:Basal Cell Carcinoma / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D002460:Cell Line; D066255:EGF Family of Proteins; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D015603:Keratinocytes / Q000473:pathology*; D007636:Keratoacanthoma / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014183:Transplantation, Heterologous
C587848:AREG protein, human; D066258:Amphiregulin; C587849:Areg protein, mouse; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins