Investigation of chemoattractant properties of various molecules in three-dimensional microenvironment to metastasis of breast cancer cells to bone

Abstract

Metastasis is the most destructive step of cancer and it is defined as spreading of tumor cells from the primary tumor cite to other organs. Because of the fact that the molecular and cellular mechanisms underlying bone metastasis have not been yet understood, the development of an effective therapy is not possible. Chemo-attractant properties of some molecules in the bone extracellular matrix has been considered among possible reasons of metastasis. In this study, collagen scaffolds were produced by electrospinning method mimicking natural porous bone structure to understand possible chemo-attractant molecules that are common in bone metastases of metastatic breast cancer cells. MCF-7 metastatic breast cancer cells' adhesion kinetics were studied on the surfaces and scaffolds which are functionalized by osteopontin, collagen type I and hydroxyapatite. Three dimensional chemotaxis slides were used for visualizing the migration. Both cell adhesion kinetics and migration results showed that collagen type 1 and hydroxyapatite combination was more effective as a chemo-attractant than only collagen type 1 in the bone metastasis of breast cancer cells. Osteopontin caused migration and cell adhesion relatively more than collagen type I; and it was showed that this protein is an effective chemo-attractant in the bone metastasis of breast cancer cells. It was shown that micro environments of the bone minerals play an important role in the formation of metastatic niche because of their support to the development and colonization of tumor cells in the bone.