Author/Editor		Schultz, Stefan; Konatschnig, Thomas; Ziegler, Stefanie; Zell, Stefanie; Kirschfink, Michael
Title		Complement resistance of tumor cells: molecular mechanisms and strategies of intervention
Translated title		Odpornost tumorskih celic za komplement: možni načini za nastanek na molekulski ravni in obeti za zdravljenje
Type		članek
Source		Med Razgl
Vol. and No.		Letnik 43, št. Suppl 5
Publication year		2004
Volume		str. 115-20
Language		eng
Abstract		Complement resistance is a common phenomenon in malignant cells impairing the immune response of cancer. Mechanisms, underlying the reduced complement sensitivity of malignant cells include the (over)expression of membrane-associated complement regulatory proteins, such as CD55 (DAF, Decay-Accelerating Factor), CD46 (MCP, Membrane Cofactor Protein) and CD59, on tumor cells. To generate a protective microenvironment, tumor cells secrete several soluble complement inhibitors and express on their surface ecto-proteases that degrade complement proteins or ecto-protein kinases, which impair the functional activity of certain complement components by phosphorylation. Understanding the complex molecular mechanisms involved in tumor cell resistance to complement is essential for the development of strategies to interfere with these evasion mechanisms and for effective targeting complement mediated cytotoxicity to cancer cells. This brief review will focus on the (over)expression of membrane-bound and soluble complement inhibitors as basal mechanisms of tumor complement resistance and give some insight in potential therapeutic approaches.
Summary		Odpornost na komplement je splošna značilnost malignih celic, ki oslabi učinkovitost imunskega odziva pri raku. Rakave celice so manj občutljive za komplement tudi zaradi povečanega izločanja membranskih beljakovin CD55 (DAF, Decay-Accelerating Factor), CD46 (MCP, Membrane Cofactor Protein) in CD59, ki so sicer pomembne za uravnavanje dejavnosti komplementnega sistema. Da bi se tumorske celice uspešno obvarovale pred imunskim sistemom, morajo okoli sebe narediti učinkovito zaščitno mikrookolje. Zato izločajo vrsto topnih zaviralcev dejavnosti komplementa, na svoji membrani izrazijo ekto-proteaze, ki razkrojijo nekatere komplementne sestavine, oz. ekto-protein-kinaze, ki s fosforilacijo oslabijo delovanje določenih sestavin komplementa. Razumevanje kompleksnosti molekularnih mehanizmov, ki imajo za posledico nastanek odpornosti tumorskih celic za komplement, je bistvenega pomena za razvoj strategije, kako preprečiti, da bi se tumorske celice uspešno obranile pred citotoksično dejavnostjo komplementa. V kratekem pregledu se bomo osredotočili na pomen povečanega izražanja na membrano vezanih in topnih inhibitorjev komplementa kot osnovnih dejavnikov pri razvoju odpornosti tumorja na komplement in o nekaterih možnostih zdravljenja raka.
Descriptors		NEOPLASMS COMPLEMENT INACTIVATORS ANTIGENS, CD55 ANTIGENS, CD59