Characterization and Signaling in a Primary Human Malignant Fibrous Histiocytoma Cell Line

ABSTRACT

Sarcomas are rare tumors, and malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma found in adults. Increasing evidence suggests a possible role for AKT activation in soft tissue sarcoma. In the present study, we established a primary human MFH cell line (named MSUMFH cells) from a fresh surgically resected MFH tumor. These cells morphologically resembled human normal fibroblasts that are the presumptive cells of origin of MFH tumor cells. As there is, unfortunately, no standard marker other than morphology to identify MFH at the cellular level, we compared MSUMFH cells to primary nonmalignant fibroblasts and the primary tumor specimen to characterize its signaling. AKT was hyperactivated in both the MSUMFH cell line and original primary MFH tumor cells compared to normal fibroblasts. The AKT hyperactivity in the MSUMFH cell line was not accompanied by activation of focal adhesion kinase (FAK) or downregulated expression of PTEN, each of which is a putative upstream regulator of AKT. In contrast, this AKT hyperactivation required PI-3K and Src in MSUMFH cells. This PI-3K and Src-dependent AKT-activated MSUMFH cell line that we established in this study may be beneficial for the future cell-based study of MFH biology.

Keywords :

• sarcoma
• malignant fibrous histiocytoma (MFH)
• Src
• AKT
• PTEN

Acknowledgments

This work was supported by National Institutes of Health Grant 2R01DK060771 (MDB). We thank Christina Downey and Jamila Power in our laboratory for their technical assistance, and Dr. Ronald Horowitz and the surgical suite and pathology staff of Sparrow Hospital for their cooperation.