Expression of hyaluronan synthase 2 or hyaluronidase 1 differentially affect the growth rate of transplantable colon carcinoma cell tumors

Abstract

Advanced colorectal cancers are often associated with elevated amounts of hyaluronan. To investigate the importance of hyaluronan in colon carcinoma tumor progression, we have expressed by stable transfection hyaluronan synthase 2 (Has2) and hyaluronidase 1 (Hyal1) in the rat colon carcinoma cell line, PROb. We found that hyaluronan overproduction led to a higher growth rate of tumor cells in vitro, and to a faster development of transplantable tumors in syngeneic rats, compared to the mock-transfectants. Has2 transfected PROb cells gave rise to tumors that were significantly less vascularized, but had a significantly larger viable tumor fraction compared to tumors generated from mocktransfectants. In contrast, Hyal1 overexpression suppressed the growth rate of tumor cells both in vitro and in vivo. Moreover, tumors derived from Hyal1-transfected cells had a significantly larger necrotic area than tumors derived from mock-and Has2-transfectants. Our study demonstrates that Has2 overproduction promotes tumorigenicity, whereas Hyal1 overexpression suppresses tumorigenicity in an experimental model for colon carcinoma.

Selective Expression and Functional Characteristics of Three Mammalian Hyaluronan Synthases in Oncogenic Malignant Transformation

“…It is therefore plausible that the HAS isoforms are involved in different stages of malignant tumor progression. Molecular cloning of the HAS genes enabled us to control HA biosynthesis and investigate HA functions in malignant transformation (23)(24)(25)(26)(27)(28)(29)(30). Overexpression of HAS2 enhanced both the anchorage-independent growth and tumorigenicity of a human fibrosarcoma cell line (24).…”

Expression of HYAL2 mRNA, hyaluronan and hyaluronidase in B‐cell non‐Hodgkin lymphoma: Relationship with tumor aggressiveness

“…Hyaluronidase levels were found to be more elevated in higher-grade cancers or in metastases from breast, brain, prostate and bladder, 3,10 -12 but recent functional studies have shown that hyaluronidase could inhibit growth of grafted tumors and metastases development. [13][14][15] …”

“…Hyaluronidase levels were found to be more elevated in higher-grade cancers or in metastases from breast, brain, prostate and bladder, 3,10 -12 but recent functional studies have shown that hyaluronidase could inhibit growth of grafted tumors and metastases development. [13][14][15] Six hyaluronidase-like genes have been described, distributed in 2 clusters on chromosomes 3 (HYAL1, -2, -3 genes) and 7 (PH-20 and the pseudogene HYALP1). 16 Recent data suggest a membrane localization for hyaluronidase-2 17 and a sequential model for HA degradation has been proposed where hyaluronidase-2 (HYAL2) would mediates the first step.…”

Structure of Human Hyaluronidase-1, a Hyaluronan Hydrolyzing Enzyme Involved in Tumor Growth and Angiogenesis,

“…The plasma HA concentration of patients with this disorder is 40-90-fold higher than in normal serum. The role of hHyal-1 in tumor progression depends on its cellular concentration; it functions as a tumor suppressor at low or very high concentration and as a tumor promoter at moderate concentration (13,(16)(17)(18).…”