Urokinase type plasminogen activator receptor (uPAR) and human epidermal growth factor receptor 2 (HER2) expression in metastasis of breast cancer

Abstract

BACKGROUND: The plasminogen urokinase activation system consists of urokinase plasminogen activator (uPA), its receptor uPAR, and plasminogen activator inhibitor type 1 (PAI-1), which are considered to have a relationship with cancer aggressiveness. Several studies have found correlations between HER2 mRNA and uPAR in disseminated tumor cells (DTCs) in breast cancer patients. They are associated with a more aggressive primary tumor phenotype and recurrence/metastasis. OBJECTIVE: This study aims to determine the relationship between the expression of urokinase-type plasminogen activator receptor (uPAR) and human epidermal growth factor receptor type 2 (HER2) with the incidence of distant metastases in breast cancer. METHODS: This study was an observational study using a cross-sectional method and was conducted at Wahidin Sudirohusodo Hospital and the network. Immunohistochemical methods carry out examination of uPAR and HER2 expression from tissues of breast cancer patients. The relationship of uPAR, HER2 expression, and metastasis was tested with the Mann Whitney test. RESULTS: The study results found that the proportion of patients with metastasis was significantly higher in high uPAR expression compared to low uPAR (77.8% compared to 36.8%). The negative HER2 expression was significantly higher in the low uPAR expression than the high uPAR (78.9% compared to 33.3%). In comparison, the positive HER2 expression was significantly higher in the high uPAR expression than the low uPAR (66.7% compared to 21.1%). In positive HER2 expression, the mean percentage of uPAR expression was significantly higher in metastases than those without metastasis (72.7% compared to 42.1%). CONCLUSIONS: uPAR expression is associated with metastasis in HER2 positive breast cancer.

Urokinase-Type Plasminogen Activator Receptor (uPAR) in Inflammation and Disease: A Unique Inflammatory Pathway Activator

“…In-depth reviews have been compiled for many of these new approaches, and thus, we have provided a broader overview. Given the recent prior reviews on uPAR-modifying treatments [ 189 , 190 , 191 , 192 , 193 , 194 ], we have provided an overview of these approaches together with a more in-depth review of the virus-derived immune-modulating serpin, Serp-1 ( Table 2 ).…”

“…The negative prognostic value with uPAR stromal expression in multiple cancer types, including colon, breast, and pancreatic cancers, clearly highlights the therapeutic potential of aiming at stromal TME as an adjuvant anti-angiogenic, anticancer treatment [ 191 , 192 , 193 , 194 ]. uPAR’s role in the tumor stromal microenvironment, overexpression in non-homeostatic tissue, high expression in aggressive cancer subtypes of poor prognosis, along with the lack of obvious cancer phenotypes when uPAR is deficient, all suggest uPAR as a candidate in anti-tumor cytotoxic therapy.…”

Functionalized liposomes for targeted breast cancer drug delivery

“…Although several protease systems have been implicated in this process, the uPA system has been identified as a central player implicated in tumor progression, metastasis, angiogenesis, cancer cell adhesion, migration, and EMT [ 276 ]. As such, the system's components are considered a diagnostic biomarker for several malignancies and cancers, including TNBC where its elevation is correlated to poor clinical outcomes, more aggressive primary tumors, metastasis, and recurrence [ 277 ].…”

uPAR is regulated via miR-561-3p and affects the progression and aggressiveness of CRC cells via the PI3K/AKT signaling pathway

“…uPAR, also known as CD87, is a glycosylphosphatidylinositolanchored protein and a multifunctional cell surface receptor that is generally located in endothelial cells, broblasts and a variety of malignant cells (Dinesh and Rasool, 2018;Liu et al, 2018;Montuori et al, 2016;Simon et al, 2021). Increasing evidence suggests that uPAR is involved in the biology of cancer cells and therefore the expression of uPAR in numerous types of cancer is of clinical importance, including in colorectal cancer (CRC) (Illemann et al, 2014;Linders et al, 2021), gastric cancer (Alpizar-Alpizar et al, 2012) and breast cancer (Smaradhania et al, 2021). uPAR has been reported to be overexpressed in different types of cancer and can regulate a variety of tumorigenic processes, including cell proliferation, migration and invasion.…”