Expression of LDL receptor-related protein 5 (LRP5) as a novel marker for disease progression in high-grade osteosarcoma

Bang H. Hoang, Tadahiko Kubo, John H. Healey, Rebecca Sowers, BethAnne Mazza, Rui Yang, Andrew G. Huvos, Paul A. Meyers, Richard Gorlick

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

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, FZDI-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.

Original languageEnglish (US)
Pages (from-to)106-111
Number of pages6
JournalInternational Journal of Cancer
Volume109
Issue number1
DOIs
StatePublished - Mar 10 2004
Externally publishedYes

Fingerprint

Low Density Lipoprotein Receptor-Related Protein-1
Osteosarcoma
Disease Progression
Reverse Transcription
Neoplasms
Wnt Proteins
Neoplasm Metastasis
Cell Line
Polymerase Chain Reaction
Human Development
Disease-Free Survival
Embryonic Development
Exons
Intercellular Signaling Peptides and Proteins
Protein Isoforms
Carcinogenesis
Necrosis
Cell Culture Techniques
Cell Proliferation

Keywords

  • Low-density lipoprotein receptor-related protein
  • Metastasis
  • Osteosarcoma
  • Survival
  • Wnt

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Expression of LDL receptor-related protein 5 (LRP5) as a novel marker for disease progression in high-grade osteosarcoma. / Hoang, Bang H.; Kubo, Tadahiko; Healey, John H.; Sowers, Rebecca; Mazza, BethAnne; Yang, Rui; Huvos, Andrew G.; Meyers, Paul A.; Gorlick, Richard.

In: International Journal of Cancer, Vol. 109, No. 1, 10.03.2004, p. 106-111.

Research output: Contribution to journalArticle

Hoang, Bang H. ; Kubo, Tadahiko ; Healey, John H. ; Sowers, Rebecca ; Mazza, BethAnne ; Yang, Rui ; Huvos, Andrew G. ; Meyers, Paul A. ; Gorlick, Richard. / Expression of LDL receptor-related protein 5 (LRP5) as a novel marker for disease progression in high-grade osteosarcoma. In: International Journal of Cancer. 2004 ; Vol. 109, No. 1. pp. 106-111.
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AU - Sowers, Rebecca

AU - Mazza, BethAnne

AU - Yang, Rui

AU - Huvos, Andrew G.

AU - Meyers, Paul A.

AU - Gorlick, Richard

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