Abstract ED01-03: Forward and backward cell transformation induced by microenvironment factors: A tribute to Allan H. Conney Free

The cancer microenvironment affects cell proliferation and growth. By using JB6 cells and a melanoma cell culture system, we have studied forward and backward cell transformation by microenvironment factors. Embryonic stem (ES)-preconditioned 3-dimensional (3-D) culture of cancer cells induces cancer cell reprogramming and results in a change in cancer cell properties such as differentiation and migration in skin melanoma. Using the ES-preconditioned 3-D microenvironment model, we provided evidence showing that the ES microenvironment inhibits proliferation and anchorage-independent growth of SK-MEL-28 melanoma cells. We also found that the ES microenvironment suppresses telomerase activity and thereby induces senescence in SK-Mel-28 cells. Furthermore, we observed that gremlin, an antagonist of BMP4, is secreted from ES cells and plays an important role in cellular senescence. Knocking down gremlin in the ES microenvironment increases proliferation and anchorage-independent growth of SK-MEL-28 melanoma cells. Taken together, these results demonstrated that gremlin is a crucial factor responsible for abrogating melanoma properties in the ES-preconditioned 3-D microenvironment.

In a collaborative effort, Dr. Allan Conney's group demonstrated that an aqueous extract of the parametrial fat pads from SKH-1 mice enhanced the conversion of JB6 P⁺ cells from an epithelial-like morphology growing in liquid medium to cells with a fibroblast-like morphology with decreased E-cadherin and increased Twist, and these cells also formed colonies in soft agar. Mechanistic studies indicated that an extract of parametrial fat stimulated the formation of reactive oxygen species in JB6 P⁺ cells. These studies provide the first in vitro demonstration of a fat tissue-induced transformation of an epithelial cell. We also showed that several microenvironmental factors can induce JB6 cell neoplastic cell transformation.

Citation Format: Zigang Dong. Forward and backward cell transformation induced by microenvironment factors: A tribute to Allan H. Conney. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr ED01-03.