Abstract

The transformation of normal cells to a malignant state has long been detected by light microscopy as visible changes in nuclear morphology. These changes include abnormal nuclear shape, increased nuclear to cytoplasmic ratio, and the presence of additional and abnormal nucleoli. Metaplasia,dysplasia, carcinoma-in-situ, and gross malignant tumors are diagnosed and graded pathologically by this traditional method. The resulting relative increase in DNA concentration within these cells produces a greater affinity for Hematoxilyn and Eosin staining, and thus, the characteristic blue color of cancerous tissues. As understanding of the cell structure expanded, the nuclear matrix emerged as an integral component of genetic processing and therefore, became an important cellular entity for study of malignant transformation. Also, several types of cancer have revealed discreet alterations in their respective nuclear matrices. One potential application of these nuclear matrix changes is development of detection and monitoring tests that would reveal the presence of abnormal cells. These tests could be utilized at a number of points in the disease process including prior to gross physical symptoms, and thereby significantly reduce patient morbidity and mortality. A second potential application of the nuclear matrix is to utilize it as a tissue specific protein targeting system to address narrowly directed therapeutic treatments, and thereby avoid the systemic side effects from broad-spectrum therapies like radiation. This paper addresses the role of the nuclear matrix in both normal cells and transformed cells, and highlights several research efforts that have advanced the ability to detect, track, and potentially treat neoplasms at the molecular level. © 2001 Wiley-Liss, Inc.