(From the November 2013 Issue of PediatricsOnline)
Scientists in in The Research Institute at Nationwide Children’s Hospital have illuminated the role of a protein that promotes tumor growth by inducing new blood vessels, enabling pediatric cancers such as osteosarcoma and neuroblastoma to thrive. The research, published in October in Cancer Research, suggests that the ΔNp63 protein leads to metastatic spread—the main cause of death in cancer patients.
For the study, Hakan Cam, PhD, senior author and a principal investigator in the Center for Childhood Cancer and Blood Diseases, and colleagues examined the expression of ΔNp63 in human cancer patients and animal models.
“Our data show that pediatric osteosarcoma and neuroblastoma express high levels of ΔNp63. Its transcripts are greatly overexpressed in about 50 percent of patient lung metastases compared to the paired primary tumor,” says Dr. Cam. “We also found that ΔNp63 is overexpressed in animal models of osteosarcoma.”
The team also evaluated the effects of up- and down-regulation of ΔNp63 in vitro to assess its role in angiogenesis, the construction of blood vessels that allows tumors to grow. Increasing ΔNp63 expression induced angiogenesis, but when its expression was inhibited, the result was a dramatic decrease in cancer cell proliferation, survival and tumorigenicity. According to Dr. Cam, if these results are also found in humans, it would make ΔNp63 a promising target for therapeutics for osteosarcoma, the second leading cause of cancer deaths in children.
“Dose-intensive chemotherapy protocols or new drugs have not substantially increased long-term survival for pediatric patients with resistant or recurrent disease over the past 20 years, so our understanding of the mechanisms underlying osteosarcoma genesis and metastasis is essential in order to improve therapy and the clinical outcomes for patients with poor prognosis,” says Dr. Cam, who adds that inhibiting ΔNp63 could suppress osteosarcoma tumor growth and enable novel and effective therapeutic approaches.
“Targeting ΔNp63 downstream effectors could radically change the current outcome for osteosarcoma patients,” he says. “In addition, these studies may reveal ΔNp63 as a valuable biomarker to identify patients who are likely to develop metastatic disease to the lung.”
Bid HK, Roberts RD, Cam M, Audino A, Kurmasheva RT, Lin J, Houghton PJ, Cam H. ΔNp63 Promotes Pediatric Neuroblastoma and Osteosarcoma by Regulating Tumor Angiogenesis. Cancer Research. 2013 Oct 23. [Epub ahead of print.]