Invasion and Metastasis Suppression by Anti-Neonatal Nav1.5 Antibodies in Breast Cancer.

Autor:	Sharudin NA; Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia., Murtadha Noor Din AH; Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia., Azahar II; Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia., Mohd Azlan M; Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia., Yaacob NS; Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia., Sarmiento ME; School of Health Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia., Dominguez AA; School of Health Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia., Mokhtar NF; Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia.
Jazyk:	angličtina
Zdroj:	Asian Pacific journal of cancer prevention : APJCP [Asian Pac J Cancer Prev] 2022 Sep 01; Vol. 23 (9), pp. 2953-2964. Date of Electronic Publication: 2022 Sep 01.
DOI:	10.31557/APJCP.2022.23.9.2953
Abstrakt:	Background: Detectable neonatal Nav1.5 (nNav1.5) expression in tumour breast tissue positive for lymph node metastasis and triple-negative subtype serves as a valid tumour-associated antigen to target and prevent breast cancer invasion and metastasis. Therapeutic antibodies against tumour antigens have become the predominant class of new drugs in cancer therapy because of their fewer adverse effects and high specificity. Objective: This study was designed to investigate the therapeutic and anti-metastatic potential of the two newly obtained anti-nNav1.5 antibodies, polyclonal anti-nNav1.5 (pAb-nNav1.5) and monoclonal anti-nNav1.5 (mAb-nNav1.5), on breast cancer invasion and metastasis. Methods: MDA-MB-231 and 4T1 cells were used as in vitro models to study the effect of pAb-nNav1.5 (59.2 µg/ml) and mAb-nNav1.5 (10 µg/ml) (24 hours treatment) on cell invasion. 4T1-induced mammary tumours in BALB/c female mice were used as an in vivo model to study the effect of a single dose of intravenous pAb-nNav1.5 (1 mg/ml) and mAb-nNav1.5 (1 mg/ml) on the occurrence of metastasis. Real-time PCR and immunofluorescence staining were conducted to assess the effect of antibody treatment on nNav1.5 mRNA and protein expression, respectively. The animals' body weight, organs, lesions, and tumour mass were also measured and compared. Results: pAb-nNav1.5 and mAb-nNav1.5 treatments effectively suppressed the invasion of MDA-MB-231 and 4T1 cells in the 3D spheroid invasion assay. Both antibodies significantly reduced nNav1.5 gene and protein expression in these cell lines. Treatment with pAb-nNav1.5 and mAb-nNav1.5 successfully reduced mammary tumour tissue size and mass and prevented lesions in vital organs of the mammary tumour animal model whilst maintaining the animal's healthy weight. mRNA expression of nNav1.5 in mammary tumour tissues was only reduced by mAb-nNav1.5. Conclusion: Overall, this work verifies the uniqueness of targeting nNav1.5 in breast cancer invasion and metastasis prevention, but more importantly, humanised versions of mAb-nNav1.5 may be valuable passive immunotherapeutic agents to target nNav1.5 in breast cancer.
Databáze:	MEDLINE
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