J. Pharm. Pharmacogn. Res., vol. 11, no. 6, pp. 926-933, Nov-Dec 2023.

DOI: https://doi.org/10.56499/jppres23.1695_11.6.926

Original Article

Check update pattern of tumorigenic vasculature signature based on MMP9 and CXCR4 expression in locally advanced breast cancer

[Comprobación del patrón de actualización de la señal de vasculatura tumorigénica basada en la expresión de MMP9 y CXCR4 en el cáncer de mama localmente avanzado]

Mochamad Bachtiar Budianto¹, Hamzah Sulaiman Lubis², Muhammad Luqman Fadli³, Wiwit Nurwidyaningtyas^4,5*

¹Department Oncology of Saiful Anwar General Hospital, Malang 65112, Indonesia.

²Department Oncology of Medan Hajj General Hospital, Sumatera Utara 20371,Indonesia.

³Department Anatomy Pathology of Saiful Anwar General Hospital, Malang 65112, Indonesia.

⁴Department Molecular and Cellular Biology, Sekolah Tinggi Ilmu Kesehatan Kendedes, Malang, 65126, Indonesia.

⁵Center for Biomedical Research, Research Organization for Health, National Research and Innovation Agency (BRIN), Genomic Building, Cibinong Science Center, Jl. Raya Bogor No. 490, Cibinong – Bogor Km. 46, Bogor, West Java, Indonesia.

*E-mail: wiwi026@brin.go.id

Abstract

Context: Locally advanced breast cancers (LABC) are the most common women malignant tumors. Appropriate vasculature is required for tumor growth support, formed by involving protein signaling, including matrix metalloprotein 9 (MMP9) and C-X-C chemokine receptor type 4 (CXCR4). Neoadjuvant chemotherapy (NAC) administration to inoperable LABC commonly exhibits a positive response, although recurrences may be encountered in a few cases.

Aims: To evaluate the MMP9 and CXCR4 expression shifting after the NAC procedure to establish evidence of the anti-angiogenic effect of NAC, which encourages knowledge of tumor size reduction pathways in LABC.

Methods: Observational designs were conducted in this study. Tissue specimens before and after NAC were collected from 45 LABC-enrolled subjects. The targeted protein expression was analyzed by immunohistochemistry, and stained sections were classified according to the percentage of nuclear-stained tumor cells. Clinicopathological features of LABC were recorded. Tumor size was measured by Vernier caliper before and after NAC.

Results: The results showed the nuclear expression of MMP9 and CXCR4 protein were observed in all tissue specimens. The expression of MMP9 and CXCR4 tended to decrease after the NAC but was not statistically significant for MMP9. There was a significant correlation between expression levels of CXCR4 and tumor size reduction (p<0.001) but not for MMP9.

Conclusions: The results of this study demonstrate the anti-angiogenic effect of NAC by inhibiting MMP9 and CXCR4, which may be integrated with tumor size reduction in LABC. Further studies are required to highlight the possibility of recurrence following inhibition of MMP9 and CXCR4 by NAC.

Keywords: breast cancers; CXCR4; MMP9; neoadjuvant chemotherapy; positive response.

Resumen

Contexto: Los cánceres de mama localmente avanzados (LABC) son los tumores malignos femeninos más frecuentes. Se requiere una vasculatura adecuada para el soporte del crecimiento tumoral, formada por la implicación de la señalización de proteínas, incluyendo la metaloproteína de matriz 9 (MMP9) y el receptor de quimioquinas C-X-C tipo 4 (CXCR4). La administración de quimioterapia neoadyuvante (NAC) al LABC inoperable suele mostrar una respuesta positiva, aunque en algunos casos pueden producirse recidivas.

Objetivos: Evaluar el cambio de expresión de MMP9 y CXCR4 tras el procedimiento NAC para establecer evidencias del efecto antiangiogénico de la NAC, lo que favorece el conocimiento de las vías de reducción del tamaño tumoral en el LABC.

Métodos: En este estudio se realizaron diseños observacionales. Se recogieron muestras de tejido antes y después de la NAC de 45 sujetos inscritos en el LABC. La expresión de la proteína diana se analizó mediante inmunohistoquímica, y las secciones teñidas se clasificaron según el porcentaje de células tumorales teñidas nuclearmente. Se registraron las características clinicopatológicas del LABC. El tamaño del tumor se midió con un calibre Vernier antes y después de la NAC.

Resultados: Los resultados mostraron la expresión nuclear de las proteínas MMP9 y CXCR4 en todas las muestras de tejido. La expresión de MMP9 y CXCR4 tendió a disminuir tras la NAC, pero no fue estadísticamente significativa para MMP-9. Se observó una correlación significativa entre los niveles de expresión de CXCR4 y la reducción del tamaño del tumor (p<0,001). Hubo una correlación significativa entre los niveles de expresión de CXCR4 y la reducción del tamaño del tumor (p<0,001), pero no para MMP9.

Conclusiones: os resultados de este estudio demuestran el efecto antiangiogénico de la NAC mediante la inhibición de MMP9 y CXCR4, que puede integrarse con la reducción del tamaño tumoral en el LABC. Se requieren más estudios para poner de relieve la posibilidad de recurrencia tras la inhibición de MMP9 y CXCR4 por NAC.

Palabras Clave: cánceres de mama; CXCR4; MMP9; quimioterapia neoadyuvante; respuesta positiva.

Citation Format: Budianto M, Lubis H, Fadli M, Nurwidyaningtyas W (2023) Check update pattern of tumorigenic vasculature signature based on MMP9 and CXCR4 expression in locally advanced breast cancer. J Pharm Pharmacogn Res 11(6): 926–933. https://doi.org/10.56499/jppres23.1695_11.6.926

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