Neutrophils activated by BJcuL, a C-type lectin isolated from Bothrops jararacussu venom, decrease the invasion potential of neuroblastoma SK-N-SH cells in vitro

 

Jessica Ohana Lemes Carneiro-Goetten1, Bruna Santos Rodrigues2, Rodrigo Amauri Nogoceke2, Thatyanne Gradowski do Nascimento1, Andrea Novais Moreno-Amaral1, Patricia Maria Stuelp-Campelo2, Selene Elifio-Esposito2

 

1 Programa de Pós-graduação em Ciências da Saúde, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, PR, Brazil.

2 Escola de Ciências da Vida, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, PR, Brazil.

 

ABSTRACT

Background: Neuroblastoma is a pediatric tumor with a mortality rate of 40% in the most aggressive cases. Tumor microenvironment components as immune cells contribute to the tumor progression; thereby, the modulation of immune cells to a pro-inflammatory and antitumoral profile could potentialize the immunotherapy, a suggested approach for high-risk patients. Preview studies showed the antitumoral potential of BJcuL, a C- type lectin isolated from Bothrops jararacussu venom. It was able to induce immunomodulatory responses, promoting the rolling and adhesion of leukocytes and the activation of neutrophils.

 

Methods: SK-N-SH cells were incubated with conditioned media (CM) obtained during the treatment of neutrophils with BJcuL and fMLP, a bacteria-derived peptide highly effective for activating neutrophil functions. Then we evaluated the effect of the same stimulation on the co-cultivation of neutrophils and SK-N-SH cells. Tumor cells were tested for viability, migration, and invasion potential.

 

Results: In the viability assay, only neutrophils treated with BJcuL (24 h) and cultivated with SK-N-SH were cytotoxic. Migration of tumor cells decreased when incubated directly (p < 0.001) or indirectly (p < 0.005) with untreated neutrophils. When invasion potential was evaluated, neutrophils incubated with BJcuL reduced the total number of colonies of SK-N-SH cells following co-cultivation for 24 h (p < 0.005). Treatment with CM resulted in decreased anchorage-free survival following 24 h of treatment (p < 0.001).

 

Conclusion: Data demonstrated that SK-N-SH cells maintain their migratory potential in the face of neutrophil modulation by BJcuL, but their invasive capacity was significantly reduced.

 

Keywords: Snake venom Neuroblastoma SK-N-SH cells C-type lectin Polymorphonuclear leukocyte Neoplasm invasion

 

Correspondence: seleneesposito@gmail.com

 

Received: 18 October 2019; Accepted: 01 April 2020; Published online: 11 May, 2020.