Mammary collagen is under reproductive control with implications for breast cancer

• DOI: 10.1016/j.matbio.2021.10.006
• Publication Date: 2021-11-25T16:32:07Z
• Authors: Qiuchen Guo; Duanchen Sun; Alexander S. Barrett; Sonali Jindal; Nathan D. Pennock; Matthew W. Conklin; Zheng Xia; Elizabeth Mitchell; Ravikant Samatham; Naomi Mirza; Steven Jacques; Sheila Weinmann; Virginia F. Borges; Kirk C. Hansen; Pepper J. Schedin
• Keywords: Lysyl Oxidase; Involution (esoterism); Collagen fiber; Breast development

Mammographically-detected breast density impacts cancer risk and progression, fibrillar collagen is a key component of density. However, physiologic factors influencing production in the are poorly understood. In female rats, we analyzed gene expression most abundantly expressed mammary collagens collagen-associated proteins across pregnancy, lactation, weaning cycle. We identified triphasic pattern regulation evidence for reproductive state-dependent composition. An initial phase deposition occurred during followed by an active suppression lactation. The third weaning-induced gland involution, which was characterized increased deposition. Concomitant changes protein abundance were confirmed Masson's trichrome staining, second harmonic generation (SHG) imaging, mass spectrometry. observed similar reproductive-state dependent patterns human tissue obtained from premenopausal women. SHG analysis also revealed structural variation cycle, with higher packing more fibers arranged perpendicular to epithelium involuting rat compared nulliparous lactating glands. Involution high cross-linking enzyme lysyl oxidase, associated levels cross-linked collagen. Breast relevance suggested, as found that diagnosed recently postpartum women displayed signatures consistent crosslinking cancers age-matched Using publicly available data sets, this involution-like, signature correlated poor progression-free survival patients overall younger sum, these findings normal may provide insight into function, etiology density, inform outcomes.