Stromal expression of invasion-promoting, matrix-degrading proteases MMP-1 and -9 and the Ets 1 transcription factor in HNPCC carcinomas and sporadic colorectal cancers.
Hereditary nonpolyposis colorectal cancers (HNPCCs) are an important subgroup of colorectal carcinomas. Compared to sporadic variants, they present several particular features, the most important of which are less invasive and metastatic properties linked to a more favorable prognosis. This contrasts to the generally poor differentiation of the epithelial tumor component. Since matrix-degrading proteases secreted by stromal fibroblasts contribute significantly to tumor invasion, we analyzed the stromal expression of 2 matrix metalloproteinases (MMP-1 and -9) and of one of their regulators, the Ets 1 transcription factor, by both immunohistochemistry and in situ hybridization in sporadic colorectal carcinomas and HNPCC tumors. We found that MMP-1 and -9 as well as Ets 1 are upregulated in the fibroblastic stroma during the development from sporadic adenomas to invasive carcinomas. HNPCC tumors exhibited a significantly lower expression of Ets 1, MMP-1 and -9. These findings on the basis of lower matrix-degrading properties of the fibroblastic tumor stroma in HNPCC tumors might help to explain why, in spite of their less differentiated phenotype, HNPCC tumors have a less invasive and metastatic potential compared to sporadic cancers.
Behrens
Peter
P
Institute of Pathology, University of Bonn, Bonn, Germany.
Mathiak
Micaela
M
Mangold
Elisabeth
E
Kirdorf
Simona
S
Wellmann
Axel
A
Fogt
Franz
F
Rothe
Marcus
M
Florin
Alexandra
A
Wernert
Nicolas
N
D000236:Adenoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000201:enzymology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D014157:Transcription Factors; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1