Hyaluronan: fundamental principles and applications in cancer

Delpech, Bertrand; Girard, Nicole; Bertrand, Pascale; Courel, Marie-Noëlle; Chauzy, Claude; Delpech, A

doi:10.1046/j.1365-2796.1997.00172.x

Cited by 146 publications

(101 citation statements)

References 39 publications

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“…In many malignancies elevated levels of hyaluronan are correlated to increased metastasis. 42,43 In the present investigation, we studied the effects of overexpression of Has2 or Hyal1 on tumor growth rate in an experimental colon carcinoma model. Transfection of carcinoma cells with Has2 cDNA led to an increase in the rate of tumor growth in syngeneic rats, whereas transfection of Hyal1 cDNA suppressed the growth rate.…”

Section: Discussionmentioning

confidence: 99%

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

Jacobson

Rahmanian

Rubin

et al. 2002

Intl Journal of Cancer

112

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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.

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Section: Discussionmentioning

confidence: 99%

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

Jacobson

Rahmanian

Rubin

et al. 2002

Intl Journal of Cancer

112

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“…There is recent evidence for a role of intracellular HA, possibly as a regulator of cell division (Evanko and Wight, 1999). With the range of effects HA can have on cell behavior, it is not surprising that abnormal levels of HA are often associated with pathological states such as osteoarthritis, rheumatoid arthritis (Engstrom- Laurent, 1997), pulmonary fibrosis, as well as a variety of malignant cancers, including lung, mammary, and hepatic carcinoma (Knudson et al, 1989;Delpech et al, 1997). HA accumulation contributes to thyroid-associated ophthalmopathy, which is associated with Graves' disease (a thyroid glandular disease) and involves remodeling of the orbital tissue (Cao et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Three vertebrate hyaluronan synthases are expressed during mouse development in distinct spatial and temporal patterns

Tien

Spicer

2005

Dev. Dyn.

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We have used in situ hybridization to study the expression of the vertebrate hyaluronan synthase (Has) gene family members, designated Has1, Has2, and Has3, during mouse development. At embryonic day (E) 7.5, Has1 and Has2 are expressed throughout the gastrulating embryo. After E8.5, Has1 expression disappears, but Has2 continues to be strongly, albeit transiently, expressed in numerous tissues, including the branchial arches and craniofacial structures such as the palatal shelves and lens pit. Has2 is also expressed during cardiac, skeletal, and tail development. Has3 transcripts are first detected at E10.5 in the maxillary and mandibular components of the first branchial arch. Notably, Has3 expression in the developing teeth, vibrissae hair follicles, nasal cavity, and inner ear complements the expression pattern of Has2. Our results indicate that, whereas Has2 is exclusively expressed in some tissues, its expression pattern overlaps and/or complements that of Has1 and Has3 in others. Developmental Dynamics 233: 130 -141, 2005.

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“…HA is expressed throughout the body including the lung mostly in areas surrounding proliferating and migrating cells and especially during inflammation and tissue repair [7]. HA is therefore believed to play an important role in both proliferation and migration of cells [8,9]. HA has recently been shown to bind to different receptors, e.g.…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic acid influence on platelet-induced airway smooth muscle cell proliferation

Holm

Bengtsson

Grenegård

et al. 2012

Experimental Cell Research

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Hyaluronic acid (HA) is one of the main components of the extracellular matrix (ECM) and is expressed throughout the body including the lung and mostly in areas surrounding proliferating and migrating cells. Furthermore, platelets have been implicated as important players in the airway remodeling process, e.g. due to their ability to induce airway smooth muscle cell (ASMC) proliferation. The aim of the present study was to investigate the role of HA, the HA-binding surface receptor CD44 and focal adhesion kinase (FAK) in plateletinduced ASMC proliferation. Proliferation of ASMC was measured using the MTS-assay, and we found that the CD44 blocking antibody and the HA synthase inhibitor 4-Methylumbelliferone (4-MU) significantly inhibited platelet-induced ASMC proliferation.The interaction between ASMC and platelets was studied by fluorescent staining of F-actin.In addition, the ability of ASMC to synthesise HA was investigated by fluorescent staining using biotinylated HA-binding protein and a streptavidin conjugate. We observed that ASMC produced HA and that a CD44 blocking antibody and 4-MU significantly inhibited platelet binding to the area surrounding the ASMC. Furthermore, the FAK-inhibitor PF 573228 inhibited platelet-induced ASMC proliferation. Co-culture of ASMC and platelets also resulted in increased phosphorylation of FAK as detected by Western blot analysis. In addition, 4-MU significantly inhibited the increased FAK-phosphorylation. In conclusion, our findings demonstrate that ECM has the ability to influence platelet-induced ASMC proliferation. Specifically, we propose that HA produced by ASMC is recognised by platelet CD44. The platelet/HA interaction is followed by FAK activation and increased proliferation of co-cultured ASMC. We also suggest that the mitogenic effect of platelets represents a potential important and novel mechanism that may contribute to airway remodelling.

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Hyaluronan: fundamental principles and applications in cancer

Cited by 146 publications

References 39 publications

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

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

Three vertebrate hyaluronan synthases are expressed during mouse development in distinct spatial and temporal patterns

Hyaluronic acid influence on platelet-induced airway smooth muscle cell proliferation

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