Low molecular weight hyaluronan inhibits colorectal carcinoma growth by decreasing tumor cell proliferation and stimulating immune response.
Hyaluronan modulates cancer progression by multiple mechanisms; nevertheless, its effects remain controversial. In this work, low molecular weight (LMW) hyaluronan but not 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 were affected 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 animals present significantly higher proliferative capacity upon stimulation with dendritic cells (DCs) pulsed with tumor lysate. Consistently, expression of MHC class II and costimulatory molecules were increased in DCs isolated from the spleen of LMW HA-treated mice. Besides, increased tumor infiltrating lymphocytes was observed in animals treated with LMW HA. Our results suggest that LMW HA in a model of CRC triggers an activation of immune system, which is likely involved in the observed tumor growth inhibition. LMW HA is suggested as a candidate molecule for therapeutic adjuvant treatments in CRC immunotherapy.
Alaniz
Laura
L
Liver Unit, School of Medicine, Austral University, Avenida Presidente Perón 1500 (B1629ODT) Derqui-Pilar, Buenos Aires, Argentina. laualaniz@yahoo.com
Rizzo
Miguel
M
Malvicini
Mariana
M
Jaunarena
Jorge
J
Avella
Diego
D
Atorrasagasti
Catalina
C
Aquino
Jorge B
JB
Garcia
Mariana
M
Matar
Pablo
P
Silva
Marcelo
M
Mazzolini
Guilermo
G
D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D006820:Hyaluronic Acid / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight
D006820:Hyaluronic Acid