Komplexita interakcií nádorového procesu
Authors:
Z. Valášková 1; S. Kiňová 2; Ľ. Danihel 3; I. Ďuriš 2; D. Markovičová 1; B. Mravec 1,4; I. Hulín 1
Authors‘ workplace:
Oddelenie klinickej patofyziológie Ústavu patologickej fyziológie Lekárskej fakulty UK Bratislava, Slovenská republika, prednosta doc. MU Dr. Marián Bernadič, CSc., mim. prof.
1; I. interná klinika Lekárskej fakulty UK a FN Bratislava, Slovenská republika, prednostka doc. MU Dr. Soňa Kiňová, PhD.
2; Ústav patologickej anatómie Lekárskej fakulty UK Bratislava, Slovenská republika, prednosta prof. MU Dr. Ľudovít Danihel, CSc.
3; Ústav experimentálnej endokrinológie SAV Bratislava, Slovenská republika, riaditeľ prof. MU Dr. Iwar Klimeš, DrSc.
4
Published in:
Vnitř Lék 2009; 55(12): 1145-1158
Category:
Reviews
Overview
Pomerne dlho pretrvávali predstavy, že nádor je tvorený iba transformovanými bunkami, pre ktoré je typická hyperproliferácia, invazívnosť a imortalizácia buniek. Terapeutické stratégie boli preto zamerané na autonómnu proliferáciu a prežívanie nádorových buniek. Ide o vlastnosti podmienené aktiváciou onkogénov a inaktiváciou tumor‑supresorových génov. Vedecké sledovania priniesli poznanie, že samotný rast nádoru je komplexným dejom. Okrem toho potvrdili účasť heterotypických multicelulárnych interakcií v nádorovom tkanive. Komplexita ako charakteristika sa priraďuje k tým dejom, ktoré nevykazujú vlastnosti lineárnych systémov. V priebehu nádorového rastu sú určité zákonitosti, ktoré nie je možné presne usporiadať z hľadiska trvania a následnosti. Preto ho môžeme považovať za dej so znakmi komplexity. Pri takomto pohľade nádorové prostredie tvoria viaceré druhy buniek, ako sú endotelové bunky a ich progenitorové bunky, pericyty, fibroblasty, fibroblasty asociované s nádorom, myofibroblasty, hladkosvalové bunky, žírne bunky, T‑ a B‑lymfocyty, neutrofily, eozinofily, bazofily, NK‑bunky a niekoľko foriem makrofágov. V súčasnosti sa opodstatnene predpokladá, že hlboké štúdium vnútorného prostredia nádorov môže viesť k formovaniu nových základov nádorovej biológie ako aj terapeutických postupov. Štúdium detailov mikroprostredia nádorov je potrebné z hľadiska vedeckého poznania a následne aj pre definovanie biomarkerov charakterizujúcich nádory. Ich sledovanie prehĺbi molekulovú diagnostiku. Biomarkery sa budú využívať v širokom meradle pre monitorovanie priebehu rastu nádorov a aj priebehu liečby. Sledovanie kombinácie biomarkerov umožní bližšie charakterizovať mikroprostredie nádorov. Okrem receptorov, signálnych molekúl, rastových faktorov, molekúl akcelerujúcich apoptózu to môžu byť nielen molekuly samotné, ale aj ich kombinácie, alebo charakteristiky neoangiogenézy, alebo inervácie nádorov. Komplexita nádorov zahrňuje nielen intracelulárne prostredie, ale aj intercelulárne vzťahy a vzťahy buniek s extracelulárnymi súčasťami nádorov. K doteraz známym skutočnostiam pribudne sledovanie cirkulujúcich nádorových buniek. Pre ich detekciu sa s veľkou pravdepodobnosťou budú využívať nízkomolekulové fluoreskujúce farbivá. Možno očakávať, že cirkulujúce nádorové bunky budú markerom prognózy i ukazovateľom progresie malignity a liečby. Vedecké bádanie prehĺbi individuálnu terapiu pacientov s nádorovými chorobami. V prehľadovej štúdii sme sa pokúsili analyzovať vedecké poznatky z pozície akceptácie zložitostí a heterogénnosti každého nádoru. Spracovanie obrovského množstva literatúry sme považovali za zmysluplné z hľadiska akceptácie nových poznatkov a teoretickej prípravy na očakávané zmeny diagnostiky a liečby nádorov. Predpokladáme, že prezentované poznatky sú užitočným krokom pre ucelený pohľad do mikroprostredia nádorov.
Kľúčové slová:
angiogenéza – inervácia nádorov – mikroprostredie nádoru – n. vagus – protizápalové pôsobenie nervového systému
Mgr. Zuzana Valášková
www.fmed.uniba.sk
e mail: zuzana.valaskova@fmed.uniba.sk
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2009 Issue 12
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