Regardless of the different genomic lesions that produce different types of cancer, there is still some common denominator or pathway that produces similar abnormalities in the structural stability of the cancer cell. This is not just the final result of cancer since it is initiated in the prenoplastic phase of all cancers and appears as an early morphological transformation event with all types of carcinogenesis (viral, chemical, or spontaneous). These structural changes occur in all human and anima tumors as well as in in vitro transformations. The pathologist can diagnosis cancer by observing these variations in cellular and nuclear structure (pleomorphism) but the causes and nature of this central feature of the cancer cell remains to be fully resolved. The proposed study is designed to apply new techniques and findings to shed insight into the chemomechanical nature and temporal dynamics of these structural changes occurring in individual live prostate cancer cells representing a wide range of metastatic potentials. It will be determined if different cell types feature specific vibratory and periodic motion or a deterministic and chaotic oscillation that could be part of an information transfer process withing the cell and how growth factors and components of the extracellular matrix might regulate these dynamic patterns and affect cellular and nuclear morphology. The nucleus is also dynamic and may also contain internal muscle-like contractile proteins and we will focus studies on a putative nuclear isoform of titin. Titin is the major protein organizing the contractile machinery of the muscle and may function in a similar role in the cell nucleus. Our investigations will utilize cell lines of the Dunning prostate cancer with wide variations in metastatic potential as well as human prostate epithelial lines that are transformed and non-transformed. From this study we will determine specific subtypes of individual cellular motion and how they correlate with cellular and nuclear shape and metastatic potential in prostate cancer cells.
