In situ detection of PCR-amplified metalloproteinase cDNAs, their inhibitors and human papillomavirus transcripts in cervical carcinoma cell lines.

This study determined whether transcription of matrix metalloproteinase (MMP)-9 and MMP-2, or tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2, or human papillomavirus (HPV) open reading frames (ORFs) is associated with invasive behavior in cervical carcinoma cells. Transforming growth factor beta1 (TGF) treatment, which significantly increased the invasive behavior of Caski cells in Matrigel when compared with treatment with epidermal growth factor, was associated with a significant increase in the percentage of cells with MMP-9 and -2 mRNA as determined by RT in situ PCR. RT in situ PCR was then used to compare directly the expression of cells invading the Matrigel with the non-invasive cells. There was a significant increase in the percentage of HeLa cells invading the Matrigel expressing MMP-9 (33%) and MMP-2 (48%) when compared with the non-invasive cells (11% and 12%, respectively); there was no significant change in the percentage of cells expressing either TIMP or HPV E6 or E7 RNA. Our data suggest that MMP-9 and -2 expression, but not TIMP or HPV expression, is an essential factor in the early stage of cervical cancer invasion.