Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, CA, USA.
Departments of Radiation Oncology and Bioengineering and Therapeutic Sciences, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, USA.
Methods Mol Biol. 2023;2614:247-260. doi: 10.1007/978-1-0716-2914-7_15.
Breast cancer progression is accompanied by profound extracellular matrix (ECM) remodeling. A greater abundance of aligned fibrillar collagen is characteristic of invasive and aggressive breast cancers and has been associated with elevated activity of collagen crosslinking enzymes, such as lysyl oxidase (LOX) and lysyl hydroxylases (LH) and the formation of more mature collagen matrix crosslinks. Aligned collagen fibers can facilitate metastatic dissemination of tumor cells, and LOX inhibitors have been used to inhibit tumor progression and metastasis in experimental models. Thus, a better understanding of how matrix crosslinking alters tumor cell phenotypes, and behaviors would improve our ability to effectively treat aggressive metastatic breast cancer. Herein described is an experimental approach to glycate and crosslink a collagen-I/basement membrane extract ECM to study the impact of ECM crosslinking on mammary tumor progression in vivo. Moreover, glycation of collagen by sugars to form advanced glycation end products naturally occurs during aging, extending the potential relevance of this approach to research on mechanisms of aging involved in disease progression.
乳腺癌的进展伴随着深刻的细胞外基质（ECM）重塑。排列整齐的纤维状胶原的丰富程度是侵袭性和侵袭性乳腺癌的特征，并与胶原交联酶（如赖氨酰氧化酶（LOX）和赖氨酰羟化酶（LH））的活性升高以及更成熟的胶原基质交联的形成有关。排列整齐的胶原纤维可以促进肿瘤细胞的转移扩散，LOX 抑制剂已被用于抑制实验模型中的肿瘤进展和转移。因此，更好地了解基质交联如何改变肿瘤细胞表型和行为将提高我们有效治疗侵袭性转移性乳腺癌的能力。本文描述了一种实验方法，即用糖使胶原蛋白-I/基底膜提取物 ECM 糖化和交联，以研究 ECM 交联对体内乳腺肿瘤进展的影响。此外，糖对胶原蛋白的糖化形成晚期糖基化终产物在衰老过程中自然发生，这使得这种方法与涉及疾病进展的衰老机制的研究相关。
