Testicular hyaluronidase induces tubular structures of endothelial cells grown in three‐dimensional colagen gel through a CD44‐mediated mechanism

Rahmanian, Mehdi; Heldin, Paraskevi

doi:10.1002/ijc.10087

Cited by 32 publications

(30 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In line with this are studies of human or bovine ECs that implicate CD44 in HA-dependent adhesion, proliferation, migration, and/or tube formation. [15][16][17][18][19][20][21][22] Somewhat surprisingly, however, treatment of mice with KM81, a bioactive anti-murine CD44 antibody, failed to consistently inhibit the neovascularization of Matrigel implants containing basic fibroblast growth factor as the angiogenic factor. 16 These results may have been related to the assay used, a possible lack of activity of KM81 against EC functions and/or compensation by RHAMM, and thus the question of CD44's involvement during in vivo angiogenesis remained an open one.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Involvement of Endothelial CD44 during in Vivo Angiogenesis

Cao

Savani

Fehrenbach

et al. 2006

The American Journal of Pathology

129

106

View full text Add to dashboard Cite

CD44, a cell-surface receptor for hyaluronan, has been implicated in endothelial cell functions, but its role in the formation of blood vessels in vivo has not been established. In CD44-null mice, vascularization of Matrigel implants and tumor and wound angiogenesis were inhibited. Leukocyte accumulation during tumor growth and wound healing in wild-type and CD44-null mice were comparable, and reconstitution of CD44-null mice with wild-type bone marrow did not restore the wild-type phenotype, suggesting that impairments in angiogenesis in CD44-deficient mice are due to the loss of endothelial CD44. Although the cell proliferation, survival, and wound-induced migration of CD44-null endothelial cells were intact, these cells were impaired in their in vitro ability to form tubes. Nascent vessels in Matrigel implants from CD44-null mice demonstrated irregular luminal surfaces characterized by retracted cells and thinned endothelia. Further, an anti-CD44 antibody that disrupted in vitro tube formation induced hemorrhage around Matrigel implants, suggesting that antagonism of endothelial CD44 undermined the integrity of the endothelium of nascent vessels. These data establish a role for CD44 during in vivo angiogenesis and suggest that CD44 may contribute to the organization and/or stability of developing endothelial tubular networks. 2). HA has also been implicated in the formation of vessels, but its effects on in vivo angiogenesis and endothelial cell (EC) function are complex and depend on HA concentration and molecular size.3 High molecular weight HA (at concentrations of Ͼ100 g/ml) inhibits EC proliferation and disrupts confluent endothelial monolayers. 4 These findings are consistent with the fact that avascular regions in chick embryo limb buds are rich in native high molecular weight HA and that expression of this form of HA in normally vascular areas results in decreased vascularity. 5 In contrast, low molecular weight HA stimulates EC proliferation, 4,6 wound-induced migration, 6 in vitro endothelial tube formation, 7 and neovascularization in chick chorioallantoic membranes 8 and cutaneous wounds. 9,10 HA mediates its biological effects through binding interactions with specific cell-associated receptors.11 A number of HA-binding proteins (so-called hyaladherins) have been identified, with CD44 and Receptor for HAMediated Motility (RHAMM) being the two best characterized cell-surface receptors for HA.2 Although several other binding interactions for CD44 and RHAMM have been reported, 12,13 currently their interactions with HA appear to be the ones most likely to directly activate intracellular signals required to stimulate processes relevant to angiogenesis.14 With respect to EC functions, previous studies have implicated CD44 in EC proliferation, migration, and adhesion to HA; RHAMM in EC motility; and both receptors in EC tube formation. [15][16][17][18][19][20][21][22] Although there is evidence for the activity of RHAMM during in vivo angiogenesis, 16 the involvement of CD44 in the formation of blood v...

show abstract

Section: Discussionmentioning

confidence: 99%

“…[15][16][17][18][19][20][21][22] Although there is evidence for the activity of RHAMM during in vivo angiogenesis, 16 the involvement of CD44 in the formation of blood vessels has not been estab-…”

mentioning

confidence: 99%

Involvement of Endothelial CD44 during in Vivo Angiogenesis

Cao

Savani

Fehrenbach

et al. 2006

The American Journal of Pathology

129

106

View full text Add to dashboard Cite

show abstract

“…It has been reported that hyaluronidase positive tumor cells induce angiogenesis in the cornea of mice, 24 and we have shown more recently that PH-20 like hyaluronidase activity induces differentiation of capillary endothelial cells in a CD44-dependent manner. 49 Therefore, carcinoma cells that possess hyaluronidase activity may be surrounded by hyaluronan fragments that induce differentiation of endothelial cells. 47,50 The mechanism behind the tumor promoting effect of hyaluronan remains to be elucidated.…”

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

Self Cite

111

View full text Add to dashboard Cite

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.

show abstract

“…22 We have recently observed that certain populations of testicular hyaluronidase induce angiogenesis in a CD44-dependent manner, and that this effect is accompanied by a decreased apoptotic rate. 17 Such an effect of hyaluronidase may also contribute to the improvement detected in liver graft viability. The expression of CD44 on endothelial cells has been reported by other laboratories 27 and us, 28 and has been shown to be involved in endothelial cell morphogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Heterotopic heart transplantations showed better morphology after daily hyaluronidase therapy compared with untreated controls, 16 and more recent studies by us revealed that hyaluronidase promotes endothelial cell morphogenesis in a CD44-dependent manner. 17 These observations prompted us to investigate the effects of testicular hyaluronidase, as a supplement to UW preservation solution, on the function and morphology of liver grafts in a rat liver transplantation model. Furthermore, the serum hyaluronan level was evaluated as an indicator of early graft function.…”

mentioning

confidence: 99%

Improvement of rat liver graft function after storage in University of Wisconsin solution containing testicular hyaluronidase

et al. 2002

Self Cite

View full text Add to dashboard Cite

Hyaluronan accumulates at sites of inflammation, which affects the organization of matrix and thereby the proliferation, migration, and adherence of cells. In this study we investigated possible beneficial effects of the hyaluronandegrading enzyme hyaluronidase on rat liver graft viability. Orthotopic rat liver transplantation was performed using a cuff technique in Wistar AL Bacharach Glaxo (WAG) rats grafted with WAG livers, which had been stored in the University of Wisconsin (UW) solution or in UW solution enriched with testicular hyaluronidase. Liver tissue architecture, as well as tissue and serum hyaluronan levels, were determined using immunohistochemistry and biochemical assays. Addition of testicular hyaluronidase (0.4 mg/mL) to livers preserved for 24 hours in cold UW solution followed by brief exposure to Ringer's lactate both prolonged the function of the grafted livers and improved their viability (4 of 10 grafts survived, compared with 0 of 10 in the control group). Hyaluronidase treatment did not damage the liver tissue architecture, and a reduced edema was observed in the survivors. Furthermore, 10 minutes after restoration of circulation, higher serum hyaluronan levels were observed in nonsuccessful compared with successful transplantations, whereas no differences in the levels of other serum viability markers were detected. We conclude that addition of testicular hyaluronidase to storage UW solution limits liver cell damage and considerably improves graft function. Furthermore, our data suggest that serum hyaluronan level is a better marker than other serum markers for early evaluation of postoperative graft function. (Liver

show abstract

Testicular hyaluronidase induces tubular structures of endothelial cells grown in three‐dimensional colagen gel through a CD44‐mediated mechanism

Cited by 32 publications

References 40 publications

Involvement of Endothelial CD44 during in Vivo Angiogenesis

Involvement of Endothelial CD44 during in Vivo Angiogenesis

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

Improvement of rat liver graft function after storage in University of Wisconsin solution containing testicular hyaluronidase

Contact Info

Product

Resources

About