Abstract:
:Chondrosarcoma is a form of malignant skeletal tumor of cartilaginous origin. The non-malignant form of the disease is termed chondroma. Correctly distinguishing between the two forms is essential for making therapeutic decisions. However, due to their similar histological appearances and the lack of a reliable diagnostic marker, it is often difficult to distinguish benign tumors from low-grade chondrosarcoma. Therefore, it is necessary to search for a potential marker that has diagnostic and prognostic values in chondrosarcoma. In this study, we demonstrated by immunohistochemistry that elevated leukemia/lymphoma-related factor (LRF) expression was associated with increased malignancy in human chondrosarcoma tissue microarrays. Moreover, siRNA depletion of LRF drastically reduced proliferation of chondrosarcoma cell lines and effectively induced senescence in these cells. This could be attributed to the observation that LRF-depleted cells were arrested at the G(1) phase, and had increased p53 and p21 expression. Moreover, LRF depletion not only drastically reduces the cellular migration and invasion potentials of chondrosarcoma cells but also sensitized these cells to the apoptosis-inducing chemotherapeutic agent doxorubicin. We conclude that LRF is a survival factor in chondrosarcomas and its expression correlates with tumor malignancy and chemoresistance. Our data implicate the potential role of LRF as both a diagnostic marker and therapeutic target for chondrosarcomas.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Kumari R,Li H,Haudenschild DR,Fierro F,Carlson CS,Overn P,Gupta L,Gupta K,Nolta J,Yik JH,Di Cesare PEdoi
10.1093/carcin/bgs254subject
Has Abstractpub_date
2012-11-01 00:00:00pages
2076-83issue
11eissn
0143-3334issn
1460-2180pii
bgs254journal_volume
33pub_type
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