Low molecular weight hyaluronan inhibits colorectal carcinoma growth by decreasing tumor cell proliferation and stimulating immune response

LAURA ALANIZ; MIGUEL RIZZO,; MARIANA MALVICINI; JORGE JAUNARENA; DIEGO ABELLA; CATALINA ATORRASAGASTI; JORGE AQUINO; MARIANA GARCÍA; PABLO MATAR; MARCELO SILVA; GUILLERMO MAZZOLINI

CANCER LETTERS

Elsevier Ireland Ltd

Año: 2009 vol. 278 p. 9 - 16

0304-3835

Hyaluronan modulates cancer progression by multiple mechanisms; nevertheless, itseffects remain controversial. In this work, low molecular weight (LMW) hyaluronan butnot high molecular weight (HMW) was found to significantly reduce colorectal carcinoma(CRC) growth in vitro and in vivo. Both survival and proliferation of CT26 tumor cells wereaffected by treatment with low doses of LMW HA, with involvement of Akt signaling mechanisms.We show for the first time that splenocytes isolated from LMW HA-treated animalspresent significantly higher proliferative capacity upon stimulation with dendritic cells(DCs) pulsed with tumor lysate. Consistently, expression of MHC class II and costimulatorymolecules were increased in DCs isolated from the spleen of LMW HA-treated mice.Besides, increased tumor infiltrating lymphocytes was observed in animals treated withLMW HA. Our results suggest that LMW HA in a model of CRC triggers an activation ofimmune system, which is likely involved in the observed tumor growth inhibition. LMWHA is suggested as a candidate molecule for therapeutic adjuvant treatments in CRCimmunotherapy.