Site-specific expression of amine oxidases in breast cancer metastases

Abstract

We aimed to evaluate the expression of amine oxidase-related proteins in metastatic breast cancer tissue and determine its clinical implication. A tissue microarray was constructed from a total of 126 metastatic breast tumors (31 bone metastases (24.6%), 36 brain metastases (28.6%), 11 liver metastases (8.7%), and 48 lung metastases (38.1%)). Immunohistochemical staining for amine oxidase-related proteins (lysyl oxidase, diamine oxidase, and monoamine oxidase A and B) was performed. In metastatic breast cancer tissue, lysyl oxidase ( p = 0.001), tumoral diamine oxidase ( p = 0.003), stromal diamine oxidase ( p = 0.047), and stromal monoamine oxidase B ( p = 0.002) were differentially expressed in different metastatic sites. Bone metastases showed low expression of lysyl oxidase, tumoral diamine oxidase, and stromal diamine oxidase. We observed high expression of lysyl oxidase in brain metastases, tumoral diamine oxidase in liver metastases, stromal diamine oxidase in lung metastases, and stromal monoamine oxidase B in bone metastases. Lysyl oxidase positivity was associated with progesterone receptor negativity ( p = 0.001), and monoamine oxidase A positivity was associated with human epidermal growth factor receptor-2 negativity ( p = 0.003) and the luminal A subtype ( p = 0.003). On univariate analysis shorter overall survival was associated with stromal diamine oxidase negativity ( p = 0.008), especially in lung metastases ( p = 0.025), and stromal monoamine oxidase B positivity ( p < 0.001). Stromal monoamine oxidase B positivity was an independent prognostic factor for shorter overall survival in multivariate Cox analysis (hazard ratio, 4.069; 95% confidence interval, 1.649-10.04; p = 0.002). Finally, in metastatic breast cancer, amine oxidase-related proteins were differentially expressed in a manner specific to metastatic site, and stromal monoamine oxidase B expression was correlated with prognosis.

Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer

“…LOX secretion from hypoxic tumors leads to collagen cross-linking at the pre-metastatic site and increases lung metastasis in TNBC models 28 . Moreover, higher LOX expression was observed in metastatic brain tumors of breast cancer patients 57 . Furthermore, Baker et al demonstrated that LOX increases cell proliferation and invasion in colorectal cancer via Src activation 58 and enhances matrix stiffness, activates FAK, leading to invasion in vitro and metastasis in vivo in colorectal cancer 59 .…”

Metal Drugs and the Anticancer Immune Response

“…In cancer, enhanced Cu levels promote tumor growth and metastasis. ,,− Importantly, Cu is an essential cofactor for endothelial cell proliferation, migration, and angiogenesis . In contrast to low levels of iron, Zn, and selenium, high levels of Cu in the blood and tumor tissues of cancer patients have been reported for a wide variety of malignancies. ,, Moreover, Cu levels in cancer were found to be indicative of the course of disease .…”

Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis

“…MAOA is overexpressed in the transition from breast cancer bone metastatic dormancy to relapse (Lu et al, 2011) and is required for breast tumor-initiating cells (Gwynne et al, 2019) and promotes prostate cancer metastasis (Wu et al, 2017). MAOB was recognized in a gene signature that characterizes mammary stem cells (Lim et al, 2010), and its expression is a prognostic factor in breast cancer (Cha et al, 2018). In addition, as noted earlier, MAOB and ALDH genes are included in a recently described single-cell LAM core signature (Guo et al, 2020).…”