[Comparison of matrix proteinase mRNA expression in morphologically normal, neoplastic, and metastatic colon tissue and colon biopsies from healthy donors]

Matrix metalloproteinases (MMPs) responsible for the extracellular matrix remodeling, the activation of various growth factors, and angiogenesis play an important role in the colorectal cancer (CRC) development. In the present work the comparative analysis of MMP-7, -8, -9, and -11 mRNA as well mRNA of the Ki-67 proliferation marker in tissue samples obtained from CRC patients and healthy individuals. Employing the real time PCR method the expression levels of several MMPs (MMP-7, -8, -9, and -11) and cell proliferation marker, Ki-67, were simultaneously measured in 256 tissue samples obtained from 112 patients with CRC: 112 samples of the primary tumor (CRC), 112 samples of the most distant border of morphologically normal colonic mucosa (MNT), 16 samples of liver metastases) and from 16 healthy volunteers who underwent colonoscopy and biopsy. The expression of both MMPs studied and Ki-67 was found to be elevated in CRC primary tumors and liver metastases compared with the normal mucosa. CRC tumor and metastatic cells exhibited similar proliferative activity. The metastases are characterized by the highest cross-correlation of MMPs among tissue types tested. For the first time it was shown that normal mucosa from healthy individuals and CRC patients varied in the MMP-8 expression level. They also had dissimilar MMP correlation patterns thus suggesting that epithelial cells adjusted to CRC tumor differ from mucosal epithelial cells of healthy individuals.Matriksnye metalloproteinazy (matrix metalloproteinases, MMP), otvechaiushchie za remodelirovanie vnekletochnogo matriksa, aktivatsiiu razlichnykh rostovykh faktorov i angiogenez, igraiut vazhnuiu rol' v razvitii kolorektal'nogo raka (KRR). V dannoĭ rabote proveden sravnitel'nyĭ analiz urovneĭ ékspressii mRNK MMP-7, -8, -9 i -11, a takzhe markera proliferatsii Ki-67 v obraztsakh tkaneĭ, poluchennykh ot patsientov s KRR i zdorovykh donorov. S ispol'zovaniem metoda PTsR v real'nom vremeni byli issledovany urovni ékspressii ikh mRNK v 256 obraztsakh tkani, poluchennykh ot 112 patsientov s KRR: 112 obraztsov pervichnoĭ tkani opukholi (KRR), 112 obraztsov morfologicheski normal'noĭ tkani slizistoĭ stenki tolstoĭ kishki (MNT), udalennoĭ ot pervichnoĭ opukholi na 15-20 sm i 16 obraztsov metastaticheskoĭ opukholi KRR v pecheni (MP). Takzhe issledovany 16 bioptatov, poluchennykh vo vremia protsedury kolonoskopii u zdorovykh volonterov (NT). Vyiavleno, chto ékspressiia mRNK genov, kodiruiushchikh MMP i Ki-67, vozrastaet v pervichnoĭ tkani KRR i MP po sravneniiu s MNT i NT. Pri étom kletki pervichnoĭ tkani opukholi i kletki metastazov imeiut skhodnuiu proliferativnuiu aktivnost'. Sredi issledovannykh tipov tkaneĭ metastaticheskaia opukhol' kharakterizuetsia naibol'shim chislom i siloĭ pozitivnykh korreliatsiĭ mezhdu urovniami ékspressii mRNK genov, kodiruiushchikh MMR. Vpervye pokazano, chto normal'naia tkan' slizistoĭ obolochki kishki patsientov s KRR i zdorovykh donorov razlichaiutsia po urovniu ékspressii mRNK MMP-8. Krome togo, oni imeiut raznye korreliatsionnye patterny issleduemykh MMR, chto svidetel'stvuet o znachitel'nykh otlichiiakh mezhdu kletkami normal'noĭ tkani, sosedstvuiushcheĭ s opukhol'iu, i kletkami slizistoĭ obolochki kishki zdorovykh donorov.