The role of extracellular matrix in non-cancerous epithelial cells and adenocarcinoma cells

Embryos and cancer share similar features such as rapid growth, active cell migration, and changes in the differentiation state. However, embryos’ highly regulated development contrasts with cancer’s aberrant growth and destructive cellular behaviour. How much are they similar and what make them different?

The pathological condition of cancer is modulated by various micro-environmental factors. The major constituent of microenvironment, extracellular matrix (ECM), surrounds tumours directly thus giving strong impact on cell growth, morphology, migration and function. ECM is mainly produced by fibroblasts, which can evolve with adjacent cancer cells to establish microenvironment which supports further cancer growth. Activation of inflammatory pathways also promotes malignant transformation, progression of the disease and metastasis. To the contrary, embryonic microenvironment does not allow grafted cancer cells to grow, despite the genetic lesions imprinted in the cells. We aim to find out the mechanism whereby embryonic microenvironment attenuates cancer-specific cellular behavior.

In order to examine microenvironmental factors, it is essential to have an in vitro system in which cancer cells readily exhibit a malignant morphology and alter their gene expression profile in response to exogenous signals. Recently my group has been successful in in vitro three-dimensional (3D) culture system. This allows us to monitor cancer cells’ morphological changes and interaction with non-cancerous cells by time-laps filming for over 72 hours (Videos 1,2). We are now studying the effect of various candidate factors on the cancer cell behavior.

Reference: Ivers, LP, Cummings B, Owolabi F, Welzel K, Klinger R, Saitoh S, O’Connor D, Fujita Y, Scholz D, Itasaki N. Dynamic and influential interaction of cancer cells with normal epithelial cells in 3D culture. Cancer Cell International 14, 108, 2014

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