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The stem and progenitor cells responsible for tissue regeneration in the adult reside in a specialized microenvironment, known as the niche, where extracellular matrix (ECM) composition and mechanical properties, such as stiffness, make an important contribution to the regulation of stem cell self-renewal and differentiation. Cells respond to the stiffness of the surrounding tissue through integrin adhesion receptors, and subsequently transduce the extracellular forces into intracellular biochemical signals in a process called mechanotransduction. The human mammary epithelium, where also breast cancer originates because of genetic alterations, is known to be exposed to variable ECM stiffness and topography during development, reproductive cycles, and malignant transformation. The PeuhuLab utilizes primary human breast tissue from reduction mammoplasty and breast cancer operations to investigate how human primary mammary epithelial cells (HMECs) and breast cancer cells interact with their environment by exerting forces and reading biomechanical cues, and how it all ties into decisions of cell fate in normal tissue homeostasis and breast cancer progression.

HMEC organoid in 3D collagen matrix

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