Hydroxyapatite Film with Distinctive Roughness for Simulating the Bone Microenvironment and Revealing the Behavior of Metastatic Mammary Cancer.

Abstract

Breast cancer is a common malignant tumor arising in normal mammary epithelial tissues. Nearly 75% of the patients with advanced mammary cancer develop bone metastases, resulting in secondary tumor growth, osteolytic bone degradation, and poor prognosis. The bone matrix comprises a highly hierarchical architecture and is composed of a nonmineral organic part, a predominantly type-I collagen, and a mineral inorganic part composed of hydroxyapatite (HA) nanocrystals (Ca10(PO4)6(OH)2). Although there has been extensive research indicating that the material properties of bone minerals affect metastatic breast cancer, it remains unclear how the microenvironment of the bone matrix, such as the roughness, which changes as a result of osteolytic bone remodeling, affects this disease. In this study, we created HA coatings in situ on polyelectrolyte multilayers (PEMs) by incubating PEMs in a mixture of phosphate and calcium ions. The HA films with distinctive roughness were successfully collected by controlling the incubation time, which served as the simulated microenvironment of the bone matrix. MDA-MB231 breast cancer cells were cultured on HA films, and an optimal roughness was observed in the adhesion, proliferation, and expression of two cytokines closely related to bone metastasis. This study contributed to the understanding of the effect of the microenvironment of the bone matrix, such as the roughness, on the metastasis behavior of breast cancer.