Type I collagen is overexpressed in medulloblastoma as a component of tumor microenvironment.
Medulloblastoma is the most common malignant brain tumor of children, and more specific and effective therapeutic management needs to be developed to improve upon existing survival rates and to avoid side-effects from current treatment. Gain of chromosome seven is the most frequent chromosome copy number aberration in medulloblastoma, suggesting that overexpression of genes on chromosome seven might be important for the pathogenesis of medulloblastoma. We used microarrays to identify chromosome seven genes overexpressed in medulloblastoma specimens, and validated using data from published gene expression datasets. The gene encoding the alpha 2 subunit of type I collagen, COL1A2, was overexpressed in all three datasets. Immunohistochemistry of tumor tissues revealed type I collagen in the leptomeninges, and in the extracellular matrix surrounding blood vessels and medulloblastoma cells. Expression of both type I collagen and the beta1 subunit of integrin, a subunit of a known type I collagen receptor, localized to the same area of medulloblastoma. Adherence of D283 medulloblastoma cells to type I collagen matrix in vitro depends on the beta1 subunit of integrin. Because medulloblastoma is characteristic of high vascularity, and because inhibition of type I collagen synthesis has been shown to suppress angiogenesis and tumor growth, our data suggest that type I collagen might be a potential therapeutic target for treating medulloblastoma.
Liang
Yu
Y
Department of Neurological Surgery, Brain Tumor Research Center, University of California-San Francisco, San Francisco, CA 94143, USA. liangy01@hotmail.com
Diehn
Maximilian
M
Bollen
Andrew W
AW
Israel
Mark A
MA
Gupta
Nalin
N
D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D003094:Collagen / Q000235:genetics* / Q000378:metabolism; D024042:Collagen Type I; D030541:Databases, Genetic; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism; D008527:Medulloblastoma / Q000235:genetics* / Q000378:metabolism; D008578:Meninges / Q000378:metabolism; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D015173:Supratentorial Neoplasms / Q000235:genetics* / Q000378:metabolism
D024042:Collagen Type I; D039641:Integrin beta Chains; D012333:RNA, Messenger; D003094:Collagen