Biomedical Chemistry: Research and Methods 2022, 5(4), e0087

MMP-9, MMP-2, VEGF and VEGFR-2 as Factors of Invasion and Angiogenesis in Squamous Cell Carcinoma of the Cervix

O.S. Timoshenko*, E.V. Kugaevskaya, T.A. Gureeva

Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Moscow 119121, Russia; *e-mail: ryzhakova.olga@list.ru

Keywords: ММP-2; ММP-9; VEGF; VEGF receptor; tumor progression; squamous cell carcinoma of the cervix

DOI:10.18097/BMCRM00187

The whole version of this paper is available in Russian.

Tissue destruction and angiogenesis play an important role in malignant tumor progression. They are responsible for the tumor growth and progress and its ability to invade and metastasize. The key role in the destructive processes belongs to matrix metalloproteinases (MMPs), which are able to cleave almost all components of the extracellular matrix (ECM). Gelatinases MMP-2 and MMP-9 hydrolyze type IV collagen, the main component of basement membranes, thereby releasing various biologically active molecules from ECM, including vascular endothelial growth factor (VEGF). VEGF is a key regulator of angiogenesis. The main mediator of the biological action of VEGF is its receptor VEGFR2. This study was aimed at assessing the relationship between the expression of the main factors of tissue destruction and angiogenesis - MMP-2, MMP-9, VEGF and VEGFR2 in the early and later stages of cervical squamous cell carcinoma (CSCC). The work was performed using samples of tumor and surrounding morphologically normal tissue, obtained from patients with or without metastases to regional lymph nodes. We have shown that MMP-9 is significantly expressed in tumors in CSCC already at the early stages of tumor progression. At later stages of the disease (when metastases to regional lymph nodes are detected in patients), the expression of MMP-2, VEGF and VEGFR2 increases markedly both in the tumor and in the morphologically normal tissue surrounding the tumor and makes an additional contribution to the processes of destruction, angiogenesis and metastasis. We assume that MMP-2, VEGF and VEGFR2 can be considered as negative markers of the course of CSCC.
Figure 1. Expression of MMP-9, MMP-2, VEGF, VEGFR 2 in tumor samples and adjacent morphologically normal tissue samples. The vertical line combines paired samples: ⊡ - tumor tissue, ◊ - morphologically normal tissue. N+ – paired tissue samples from group No. 1 (taken from patients with metastases in regional lymph nodes), N- – paired tissue samples from group No. 2 (taken from patients without metastases).
Figure 2. Expression of MMP-9, MMP-2, VEGF, VEGFR2 in cervical squamous cell carcinoma samples. Magnification ×400. Reaction intensity 3+ - samples A1, A2, B1, C1; reaction intensity 2+ - sample D1; reaction intensity 1+ - samples B1, C1; reaction intensity 0 - sample D1.

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Table 1. Characteristics of clinical material. Data obtained from patients medical history.

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Table 2. Primers sequence used in the work.

FUNDING

The work was performed within the framework of the Program for Basic Research in the Russian Federation for a long-term period (2021-2030) (№ 122022800499-5).

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