The tumor microenvironment: possible role of integrins and the extracellular matrix in tumor biological behavior of intratubular germ cell neoplasia and testicular seminomas.
In the present study, we examined the distribution of integrin subunits and extracellular matrix proteins in normal testis, intratubular germ cell neoplasia (ITGCN), and primary and metastatic seminomas. Compared to normal testis in ITGCN, Sertoli cells showed increased expression of alpha 3, alpha 6, and beta 1 integrin subunits. Malignant intratubular germ cells stained for alpha 3, alpha 6, and beta 1 integrin subunits. Progression of ITGCN to invasive seminoma was associated with loss of alpha 3 integrin subunit expression by tumor cells. Consequent to this loss, it can be speculated that the strong expression on ITGCN may be related to the noninvasive character of the lesion as is also known from other noninvasive tumors. All tumors showed a strong expression of alpha 6 and beta 1 integrin subunits. The alpha 5 integrin subunit was weakly expressed in primary seminomas in all stages. No differences were observed in integrin expression between primary and metastatic tumors. The distribution of extracellular matrix proteins was heterogeneous and revealed clear architectural differences between seminomas that may reflect different stages of tumor stroma formation. To our knowledge, the results presented in this study provide the first information on the possible role of tumor-extracellular matrix interactions in the biological behavior of ITGCN and testicular seminomas.
Timmer
A
A
Department of Pathology, University Hospital Groningen, The Netherlands.
Oosterhuis
J W
JW
Schraffordt Koops
H
H
Sleijfer
D T
DT
Szabo
B G
BG
Timens
W
W
D016326:Extracellular Matrix Proteins / Q000032:analysis*; D018237:Germinoma / Q000737:chemistry* / Q000473:pathology; D006801:Humans; D016023:Integrins / Q000032:analysis*; D008297:Male; D018239:Seminoma / Q000737:chemistry* / Q000473:pathology / Q000556:secondary; D013736:Testicular Neoplasms / Q000737:chemistry* / Q000473:pathology; D013737:Testis / Q000737:chemistry*
D016326:Extracellular Matrix Proteins; D016023:Integrins