Journal Facts

Journal
BoneKEy Reports
ISSN
2047-6396
Volume
2
Year
2013

Article Facts

Title
CD44: evidence for its role in osteosarcoma morbidity and mortality
DOI
10.1038/bonekey.2013.51
Author
Online Date
03/13/2013

Article Links

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CD44: evidence for its role in osteosarcoma morbidity and mortality


DOI:10.1038/bonekey.2013.51

The molecular mechanisms that are responsible for CD44-induced chemoresistance in osteosarcoma are unknown. In carcinoma (breast, ovary, colon), glioma or lymphoma, hyaluronic acid (HA)–CD44 interaction mediates chemoresistance through different pathways, according to the type of tumor studied. In this respect, CD44 is associated with the expression of drug transporters (e.g. MDR1, MRP2, etc.) and the activation (or inhibition) of different signaling pathways (Src, Twist, Lyn, Akt, Hippo).

In this study, Gvozdenovic et al. showed that osteosarcoma patients with high levels of CD44 expression tended to have shorter overall survival (p<0.08), but this failed to reach significance as an independent predictor of outcome. Prognosis was, however, significantly worse in patients with high CD44 levels and lung metastases.

The authors suggest that the association between CD44 levels and outcome may be explained by increased chemoresistance, mediated by HA. To test their hypothesis, they generated an orthotopic mouse model of osteosarcoma, which showed that CD44 overexpression in SaOS-2 cells led to a higher risk of both primary tumors and metastatic tumors in the lungs, an effect that was HA-dependent in both cases.

Editor’s comment: This study provides strong experimental evidence that CD44–HA interaction enhances lung metastasis and the chemoresistance of SaOs-2 osteosarcoma cells. It will be interesting to determine which of these mechanisms confer chemoresistance in HA–CD44-activated osteosarcoma cells.

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