title: Low molecular weight hyaluronan inhibits colorectal carcinoma growth by decreasing tumor cell proliferation and stimulating immune response.
abstract: 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.
authors.affiliation: Liver Unit, School of Medicine, Austral University, Avenida Presidente Perón 1500 (B1629ODT) Derqui-Pilar, Buenos Aires, Argentina. laualaniz@yahoo.com
authors.forename: Laura
authors.initials: L
authors.lastname: Alaniz
authors.forename: Miguel
authors.initials: M
authors.lastname: Rizzo
authors.forename: Mariana
authors.initials: M
authors.lastname: Malvicini
authors.forename: Jorge
authors.initials: J
authors.lastname: Jaunarena
authors.forename: Diego
authors.initials: D
authors.lastname: Avella
authors.forename: Catalina
authors.initials: C
authors.lastname: Atorrasagasti
authors.forename: Jorge B
authors.initials: JB
authors.lastname: Aquino
authors.forename: Mariana
authors.initials: M
authors.lastname: Garcia
authors.forename: Pablo
authors.initials: P
authors.lastname: Matar
authors.forename: Marcelo
authors.initials: M
authors.lastname: Silva
authors.forename: Guilermo
authors.initials: G
authors.lastname: Mazzolini
mesh_terms: 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
chemical_list: D006820:Hyaluronic Acid