Expression and the molecular forms of neutrophil gelatinase‐associated lipocalin and matrix metalloproteinase 9 in canine mammary tumours

Abstract

Neutrophil gelatinase‐associated lipocalin (NGAL) is a new biomarker for renal injury. It is also involved in tumorigenesis of different human cancer types. The oncogenic role of NGAL is related to its molecular forms, and heterodimer formation with matrix metalloproteinase 9 (MMP9) promotes human breast cancer (HBC) invasion and metastasis. To date, the levels of NGAL and NGAL/MMP9 complex have not yet been explored in canine mammary tumours (CMTs). Hence, this study aimed to investigate whether NGAL and its molecular forms could be the biomarker for CMT diagnosis. To this end, expression profile of NGAL and MMP9 in mammary epithelial cells as well as in urine samples were detected. By immunohistochemistry staining, NGAL was expressed at variable levels. Unlike HBC, a significant reduction in NGAL expression was demonstrated in benign and malignant CMTs as compared with normal controls. Additionally, NGAL expression was significantly reduced in dogs with metastatic CMTs. By contrast, the mean score of MMP9 expression in ascending order was normal groups, benign, and malignant CMTs. Interestingly, analysis of the molecular form revealed the NGAL/MMP9 complex presents in most mammary tissues and urine of dogs with benign or malignant CMTs, whereas the complex was absent in samples from dogs without CMTs. In conclusion, NGAL and MMP9 are ubiquitously expressed in canine mammary epithelial cells in normal and cancerous status. However, the NGAL/MMP9 complex exclusively presents in mammary tissues and urine of dogs with tumours.

Determination of FABP4, RBP4 and the MMP‑9/NGAL complex in the serum of women with breast cancer

“…NGAL expression is regarded as a considerable diagnostic and prognostic biomarker in several diseases, including inflammation and tumor growth (29,31,34). It is noteworthy that NGAL generates a complex with metalloproteinase-9 (MMP-9) that constraints MMP-9 autodegradation and subsequently leads to increased activity of MMP-9 (31,(34)(35)(36). Previous studies have suggested that MMP-9/NGAL complex augments cancer growth, including breast cancer (29,31,(34)(35)(36).…”

“…It is noteworthy that NGAL generates a complex with metalloproteinase-9 (MMP-9) that constraints MMP-9 autodegradation and subsequently leads to increased activity of MMP-9 (31,(34)(35)(36). Previous studies have suggested that MMP-9/NGAL complex augments cancer growth, including breast cancer (29,31,(34)(35)(36). MMP-9 is found in gelatinase granules and contribute to cancer progression, invasion and metastasis in numerous neoplastic diseases (29,37,38).…”

“…The relationship of the corresponding proteins with the development of breast disease was further examined considering the molecular classification of breast cancer into different molecular subtypes (34,35). Hence, the examined cases were classified into two major groups, containing the Luminal cohort (Luminal A and Luminal B) and TN/HER-2 group (HER-2 positive and Triple Negative).…”

Farklı Tipteki Köpek Meme Karsinomlarında PCNA ve MMP-9 Ekspresyonlarının İmmunohistokimyasal Olarak Değerlendirilmesi

“…Chen et al 2019 (10) found that malignant canine breast tumors express MMP-9 at a higher rate than normal breast tissues. Nowak et al 2008 (29) detected MMP-9 positive reaction in 83% of the cases in their study with tissue samples taken from 35 canine mammary carcinomas.…”

Current invasive and non-invasive biomarkers in canine mammary tumors

“…Besides, studies indicate that accumulation of NGAL is associated with the progression of the tumor (Fernandez et al, 2005;Provatopoulou et al, 2009). Three molecular forms of NGAL complexed with Matrix Metalloproteinase 9 (MMP9) are identified which are monomer (25-kDa), homodimer (45-kDa) and heterodimer (135-kDa) (Chen et al, 2019). MMP9 is an enzyme which participates in the initiation, growth, metastasis, and progression of the tumor (Gialieli et al, 2011).…”