Blocking podoplanin suppresses growth and pulmonary metastasis of human malignant melanoma

• Published in: BMC cancer Vol. 19; no. 1; p. 599
• Main Authors: Xu, Mengqiao, Wang, Xia, Pan, Yanfang, Zhao, Xingpeng, Yan, Bin, Ruan, Changgeng, Xia, Lijun, Zhao, Yiming
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 17.06.2019; BioMed Central; BMC
• Subjects: Animals; Antibodies; Antibody-based therapy; Antineoplastic Agents, Immunological - pharmacology; Blood clots; Blood platelets; Brain cancer; Cancer; Cancer metastasis; Cancer research; Cancer treatment; Cell Line, Tumor; Cell Proliferation - drug effects; CHO Cells; Cricetulus; EDTA; Ethics; Female; Flow cytometry; Genetic aspects; Glycoproteins; Humans; Immunoglobulin G; Immunoglobulins; Lectins; Lectins, C-Type - metabolism; Lung cancer; Lung Neoplasms - metabolism; Lungs; Malignant melanoma; Medical prognosis; Melanoma; Melanoma - metabolism; Membrane Glycoproteins - antagonists & inhibitors; Membrane Glycoproteins - metabolism; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Monoclonal antibodies; Nasopharyngeal cancer; Nasopharyngeal Neoplasms - metabolism; Neoplasm Metastasis; Platelet aggregation; Platelet Aggregation - drug effects; Podoplanin; Signal Transduction - drug effects; Skin cancer; Tumor Burden; Tumor growth; Tumors; Xenograft Model Antitumor Assays; Xenografts; United Kingdom > UK; United States > US; China; Metastasis; Tumor growth; Antibody-based therapy; Malignant melanoma; Podoplanin
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-019-5808-9

Podoplanin (PDPN), a transmembrane O-glycoprotein, is up-regulated in many tumors and is involved in tumor metastasis and malignant progression. In previous studies, we generated a functional blocking monoclonal antibody (mAb, SZ168) against the extracellular domain of human PDPN. This study is aimed to investigate whether blocking PDPN by SZ168 inhibits tumor growth and metastasis. Malignant melanoma xenograft model by inoculating subcutaneously human malignant melanoma cell line C8161 into the back of BALB/c nude mice was used. Endogenous PDPN expression in C8161 cells and nasopharyngeal cancer cell line CNE-2 was detected using western blot and flow cytometry. SZ168 significantly inhibited C8161 or CNE-2 cell-induced platelet aggregation in a dose-dependent manner with a maximal inhibition of 73.9 ± 3.0% in C8161 cells or 77.1 ± 2.7% in CNE-2 cells. Moreover, SZ168 inhibited the growth and pulmonary metastasis of C8161cells in vivo. The number of lung metastatic foci in the SZ168-treated group was significantly decreased compared with that in the control mouse IgG group (1.61 ± 0.44 vs.3.83 ± 0.60, P < 0.01). Subcutaneous tumor volume, weight, and incidence were also significantly reduced in the SZ168-treated group compared to the control group (P < 0.05). Additionally, SZ168 recognized PDPN in immunohistochemical analyses of tumor tissue sections. SZ168 blocks growth and pulmonary metastasis of human malignant melanoma by inhibiting the interaction between tumor PDPN and platelet CLEC-2 and therefore is a promising antibody for therapeutic development against malignant melanoma.