As some of the brightest minds in the scientific community continue their fight to cure cancer, assistant professor Weihua "John" Zhang is contributing from the state-of-the-art labs housed in the UH Center for Nuclear Receptors and Cell Signaling (CNRCS). His most recent study of cancer cell lines and the multinucleated cells (MNCs) found within those lines was published in the March 1 issue of Cancer, the official scientific journal of the American Cancer Society.

Cancer cell lines are one of the most widely relied-upon tools in cancer research; however, the origin of MNCs found within those cell lines has never been clear. After evaluating the relationship between MNCs and cancer cell lines, Zhang determined that MNCs are highly resistant to chemotherapy, and that a single MNC is capable of forming a solid tumor. Given their malicious capabilities and resistance to treatment, MNCs are a significant piece of the cancer research puzzle, similar to how stem cells yield information about the origins of disease and new methods of treatment.

"Patient killing cancer cells have two distinct features, resistance to therapy and high potency for tumorigenesis," said Zhang. "The multinucleated tumor cells possess these features, and understanding the molecular mechanisms on which these cells depend for survival may allow us to find novel targets for more effective therapies."

The results of Zhang's study showed that lab mice injected with a single MNC produced a tumor at the site of each injection. Further examination found that the tumors were specific to metastatic cancers. Metastasis is most commonly recognized as the cause of death in patients with malignant solid tumors. The core molecular mechanism of metastasis still remains largely unknown.

Over the course of the 18-month study, Zhang also observed that the MNCs originated from a rare subpopulation of mononuclear cells that are capable of self-renewal and asymmetric division. Such processes enable the cells' resistance to chemotherapy. However, the growth of MNCs may be arrested under stress, indicating a potential treatment pathway.

The study was conducted in collaboration with Dr. Isaiah Fidler, of the M.D. Anderson Cancer Center, and was supported in part by the UH Center for Nuclear Receptors and Cell Signaling, a Cancer Center Support Core Grant and a grant from the National Cancer Institute of the National Institutes of Health.

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