Elevated Collagen XIII Levels Linked to Breast Cancer Metastasis

Anoikis is a form of programmed cell death that occurs in anchorage-dependent cells when they detach from the surrounding extracellular matrix (ECM). Usually cells stay close to the tissue to which they belong since the communication between proximal cells as well as between cells and ECM provide essential signals for growth or survival. When cells are detached from the ECM, there is a loss of normal cell–matrix interactions, and they may undergo anoikis. However, metastatic tumor cells may escape from anoikis and invade other organs. Cancer cells develop anoikis resistance by several mechanisms, including changes in integrin and matrix signaling, metabolic deregulation, and stress responses of cancer cells.

Investigators at the University of Kentucky (Lexington, USA) analyzed the association of collagen XIII expression with breast cancer development and metastasis using published gene expression profiles generated from human breast cancer tissues, and the used mouse models to investigate roles of collagen XIII in regulating invasive tumor growth. They also inhibited collagen XIII signaling with beta-1 integrin function-blocking antibody.

Integrins are transmembrane receptors that facilitate cell- ECM adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, organization of the intracellular cytoskeleton, and movement of new receptors to the cell membrane.

Results published in the October 1, 2018, online edition of the journal Breast Cancer Research revealed that expression of collagen XIII was higher in breast cancer tissue compared with normal mammary gland, and that the increased mRNA level of collagen XIII in cancer tissue was associated with poor prognosis and cancer metastasis. They also demonstrated that collagen XIII expression enhanced cancer stem cell-like behavior and invasive tumor growth through beta-1 integrin. Importantly, silencing collagen XIII in breast cancer cells significantly reduced cancer metastasis.

“Understanding how these cancer cells spread and colonize distant organs is crucial for identifying novel strategies to halt the cancer progression and improve cancer treatment,” said senior author Dr. Ren Xu, associate professor pharmacology and nutritional sciences at the University of Kentucky.

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