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Expression of LDL receptor‐related protein 5 (LRP5) as a novel marker for disease progression in high‐grade osteosarcoma
Author(s) -
Hoang Bang H.,
Kubo Tadahiko,
Healey John H.,
Sowers Rebecca,
Mazza BethAnne,
Yang Rui,
Huvos Andrew G.,
Meyers Paul A.,
Gorlick Richard
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11677
Subject(s) - lrp5 , wnt signaling pathway , cancer research , biology , autocrine signalling , carcinogenesis , paracrine signalling , osteosarcoma , medicine , receptor , signal transduction , cancer , microbiology and biotechnology , genetics
The Wingless‐type (Wnt) family of proteins and its coreceptor LRP5 have recently been implicated in human skeletal development. Wnt pathway modulates cell fate and cell proliferation during embryonic development and carcinogenesis through activation of receptor‐mediated signaling. Osteosarcoma (OS) is a bone‐forming tumor of mesenchymal origin whose growth control has been linked to autocrine or paracrine stimulation by several growth factor families. We examined 4 OS cell lines for WNT1 , WNT4 , WNT5A , WNT7A , WNT11 , FZD1‐10 and LRP5 expression by reverse transcription polymerase chain reaction (RT‐PCR). In addition, RT‐PCR for LRP5 expression was performed in 44 OS patient samples and the findings were correlated with clinical data. Expression profiling of Wnts and their receptors revealed the presence of several isoforms in OS cell lines. Overall, 22/44 (50%) of OS patient samples showed evidence of LRP5 expression. Presence of LRP5 correlated significantly with tumor metastasis ( p = 0.005) and the chondroblastic subtype of OS ( p = 0.045). In addition, patients whose tumors were positive for LRP5 showed a trend toward decreased event‐free survival ( p = 0.066). No significant association was found between LRP5 expression and age, gender, site of disease, site of metastasis or degree of chemotherapy‐induced tumor necrosis. Sequencing of exon 3 of LRP5 in 10 OS patient‐derived cell cultures showed no activating mutation of LRP5 . These results showed that expression of LRP5 is a common event in OS and strongly suggest a role for LRP and Wnt signaling in the pathobiology and progression of this disease. © 2003 Wiley‐Liss, Inc.