Recent Advances in the Aging Microenvironment of Breast Cancer

Abstract

Aging is one of the risk factors for advanced breast cancer. With the increasing trend toward population aging, it is important to study the effects of aging on breast cancer in depth. Cellular senescence and changes in the aging microenvironment in vivo are the basis for body aging and death. In this review, we focus on the influence of the aging microenvironment on breast cancer. Increased breast extracellular matrix stiffness in the aging breast extracellular matrix can promote the invasion of breast cancer cells. The role of senescence-associated secretory phenotypes (SASPs) such as interleukin-6 (IL-6), IL-8, and matrix metalloproteases (MMPs), in breast cancer cell proliferation, invasion, and metastasis is worthy of exploration. Furthermore, the impact of senescent fibroblasts, adipocytes, and endothelial cells on the mammary matrix is discussed in detail. We also list potential targets for senotherapeutics and senescence-inducing agents in the aging microenvironment of breast cancer. In conclusion, this review offers an overview of the influence of the aging microenvironment on breast cancer initiation and progression, with the aim of providing some directions for future research on the aging microenvironment in breast cancer.

The role of DYNLT3 in breast cancer proliferation, migration, and invasion via epithelial‐to‐mesenchymal transition

“…[12][13][14] An increase in the rigidity of the breast ECM with aging promotes the tumor cells invasion and stimulates the secretion of proliferation-associated cytokines. 15 Breast cancer cells interact with senescent cells that progressively accumulate unfavorable mutations, leading to tumor progression and metastasis. 15 However, the detailed mechanisms involved in age-induced breast cancer occurrence and progression is limited.…”

“…15 Breast cancer cells interact with senescent cells that progressively accumulate unfavorable mutations, leading to tumor progression and metastasis. 15 However, the detailed mechanisms involved in age-induced breast cancer occurrence and progression is limited.…”

“…The promoting effect of age in breast tumorigenesis and cancer development is caused by the successive accumulation of genetic and epigenetic alterations in mammary epithelial cells and the tumor microenvironment 12–14 . An increase in the rigidity of the breast ECM with aging promotes the tumor cells invasion and stimulates the secretion of proliferation‐associated cytokines 15 . Breast cancer cells interact with senescent cells that progressively accumulate unfavorable mutations, leading to tumor progression and metastasis 15 .…”