Ability to stimulate angiogenesis/lymphangiogenesis is recognized as an inherent feature of cancer cells providing necessary conditions for their growth and dissemination. "Angiogenic switch" is one of the earliest consequences of malignant transformation that encompasses a great number of genes and triggers a complex set of signaling cascades in endothelial cells. The processes of tumor microvasculature development are closely connected to the steps of carcinogenesis (from benign lesions to invasive forms) and occur through multiple deviations from the norm. Analysis of expression of proangiogenic factors at successive steps of cervical cancer development (intraepithelial neoplasia, cancer in situ, microinvasive, and invasive cancer) enables to reconstruct the regulatory mechanisms of (lymph-)angiogenesis and to discriminate the most important components. This review presents detailed analysis of literature data on expression of the key regulators of angiogenesis in cervical intraepithelial neoplasia and cervical cancer. Their possible involvement in molecular mechanisms of neoplastic transformation of epithelial cells, as well as invasion and tumor metastasis is discussed. Correlation between expression of proangiogenic molecular factors and various clinicopathological parameters is considered, the potential of their use in molecular diagnostics and targeted therapy of cervical cancer is reviewed. Particular attention is paid to relatively poorly studied regulators of lymphangiogenesis and "non-VEGF dependent", or alternative, angiogenic pathways that constitute the prospect of future research in the field.
Sposobnost' stimulirovat' angiogenez/limfangiogenez priznana neot"emlemym svoĭstvom rakovykh kletok, obespechivaiushchim ikh neobkhodimymi usloviiami dlia rosta i metastazirovaniia. “Angiogennoe perekliuchenie” – odno iz naibolee rannikh sledstviĭ zlokachestvennoĭ transformatsii, okhvatyvaiushchee bol'shoe chislo genov i zapuskaiushchee slozhnuiu sovokupnost' signal'nykh kaskadov v kletkakh éndoteliia. Protsessy formirovaniia mikrososudistoĭ seti opukholi tesno sopriazheny s étapami kantserogeneza (ot vozniknoveniia dobrokachestvennykh izmeneniĭ do invazivnykh form) i protekaiut s mnogochislennymi otkloneniiami ot normy. Analiz urovnia ékspressii proangiogennykh faktorov pri posledovatel'nykh étapakh razvitiia raka sheĭki matki (intraépitelial'nye neoplazii, rak in situ, mikroinvazivnyĭ i invazivnyĭ rak) daet vozmozhnost' rekonstruirovat' reguliatornye mekhanizmy angiogeneza/limfangiogeneza i vydelit' sredi nikh naibolee vazhnye komponenty. V obzore obobshcheny dannye literatury po ékspressii kliuchevykh reguliatorov angiogeneza pri tservikal'nykh intraépitelial'nykh neoplaziiakh i rake sheĭki matki, obsuzhdaetsia ikh vozmozhnoe uchastie v mekhanizmakh transformatsii épitelial'nykh kletok, invazii i metastazirovanii. Rassmotrena vzaimosviaz' urovnia ékspressii proangiogennykh molekuliarnykh faktorov s razlichnymi kliniko-patologicheskimi parametrami i vozmozhnost' ikh ispol'zovaniia v diagnostike i targetnoĭ terapii raka sheĭki matki. Osoboe vnimanie udeliaetsia sravnitel'no maloizuchennym reguliatoram limfangiogeneza i “ne-VEGF zavisimym”, al'ternativnym, putiam aktivatsii angiogeneza, sostavliaiushchim perspektivu dal'neĭshikh issledovaniĭ v dannoĭ oblasti.
Keywords: angiogenesis; cervical cancer; intraepithelial neoplasia; lymphangiogenesis; transcription factors; vascular growth factors.