Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Substantial myxoid change can occur in malignant melanoma, but its importance in primary disease has not been systematically evaluated. This report describes the clinical, microscopic, histochemical, and immunohistochemical findings in 12 patients with primary cutaneous malignant melanoma with myxoid features. The tumors presented as solitary lesions situated on the limbs (six lesions), trunk (four lesions), and head and neck (two lesions). The patients included six women and six men, whose ages ranged from 26 to 95 years, with a mean of 63 years. Breslow thickness varied from 0.48 mm to more than 12 mm, with a mean of more than 3.2 mm. Clinical follow-up for an average of 22 months showed one local recurrence, but no evidence of metastases yet. In all cases, there was a combination of myxoid and nonmyxoid areas. A minimum of 15% myxoid cross-sectional area was required for inclusion in the study, and up to 80% was observed. The pale blue mucin identified on hematoxylin and eosin staining was sensitive to hyaluronidase and positive for alcian blue in the 10 cases stained. Immunohistochemical staining was positive for S-100 in all 9 cases stained, positive for HMB-45 in 9 (90%) of 10, and negative for cytokeratin in all 9 cases in which myxoid melanoma remained in the block after previous sections. The presence of myxoid stroma did not define a biologically significant subgroup of melanoma. Only in cases with extensive (>50%) myxoid stromal effacement of the melanoma was there a major diagnostic hurdle. The diagnosis of primary cutaneous melanoma with myxoid features was seldom as problematic as metastatic myxoid melanoma. Positive S-100 stains, negative cytokeratin immunohistochemical stains, and hyaluronidase-sensitive alcian blue staining assisted in the diagnosis of this entity.
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PMID:Cutaneous melanoma with myxoid features: twelve cases with differential diagnosis. 1058 4

BMP4/7-dependent expression of inhibitor of differentiation/DNA binding (Id) proteins 1 and 3 has been implicated in tumor progression and poor prognosis of malignant melanoma patients. Hyaluronic acid (HA), a pericellular matrix component, supports BMP7 signalling in murine chondrocytes through its receptor CD44. However, its role in regulating BMP signalling in melanoma is not clear. In this study we found that depletion of endogenously-produced HA by hyaluronidase treatment or by inhibition of HA synthesis by 4-methylumbelliferone (4-MU) resulted in reduced BMP4/7-dependent Id1/3 protein expression in mouse melanoma B16-F10 and Ret cells. Conversely, exogenous HA treatment increased BMP4/7-dependent Id1/3 protein expression. Knockdown of CD44 reduced BMP4/7-dependent Id1/3 protein expression, and attenuated the ability of exogenous HA to stimulate Id1 and Id3 expression in response to BMP. Co-IP experiments demonstrated that CD44 can physically associate with the BMP type II receptor (BMPR) ACVR2B. Importantly, we found that coordinate expression of Id1 or Id3 with HA synthases HAS2, HAS3, and CD44 is associated with reduced overall survival of cutaneous melanoma patients. Our results suggest that HA-CD44 interactions with BMPR promote BMP4/7-dependent Id1/3 protein expression in melanoma, contributing to reduced survival in melanoma patients.
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PMID:Hyaluronic acid-CD44 interactions promote BMP4/7-dependent Id1/3 expression in melanoma cells. 3182 66