1. Inicio
  2. Publicaciones
  3. High VEGFR3 Expression Reduces Doxorubicin Efficacy in Triple-Negative Breast Cancer

High VEGFR3 Expression Reduces Doxorubicin Efficacy in Triple-Negative Breast Cancer

Fecha de publicación: Fecha Ahead of Print:

Autores de INCLIVA

Participantes ajenos a INCLIVA

  • Rojo, Federico
  • Madoz-Gurpide, Juan

Grupos y Plataformas de I+D+i

Abstract

Due to the lack of specific targets, cytotoxic chemotherapy still represents the common standard treatment for triple-negative breast patients. Despite the harmful effect of chemotherapy on tumor cells, there is evidence that treatment could modulate the tumor microenvironment in a way favoring the propagation of the tumor. In addition, the lymphangiogenesis process and its factors could be involved in this counter-therapeutic event. In our study, we have evaluated the expression of the main lymphangiogenic receptor VEGFR3 in two triple-negative breast cancer in vitro models, resistant or not to doxorubicin treatment. The expression of the receptor, at mRNA and protein levels, was higher in doxorubicin-resistant cells than in parental cells. In addition, we confirmed the upregulation of VEGFR3 levels after a short treatment with doxorubicin. Furthermore, VEGFR3 silencing reduced cell proliferation and migration capacities in both cell lines. Interestingly, high VEGFR3 expression was significantly positively correlated with worse survival in patients treated with chemotherapy. Furthermore, we have found that patients with high expression of VEGFR3 present shorter relapse-free survival than patients with low levels of the receptor. In conclusion, elevated VEGFR3 levels correlate with poor survival in patients and with reduced doxorubicin treatment efficacy in vitro. Our results suggest that the levels of this receptor could be a potential marker of meager doxorubicin response. Consequently, our results suggest that the combination of chemotherapy and VEGFR3 blockage could be a potentially useful therapeutic strategy for the treatment of triple-negative breast cancer.

Datos de la publicación

ISSN/ISSNe:
1661-6596, 1422-0067

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES  MDPI AG

Tipo:
Article
Páginas:
-
PubMed:
36835014

Citas Recibidas en Web of Science: 4

Documentos

Métricas

Filiaciones mostrar / ocultar

Keywords

  • VEGFR3; triple-negative breast cancer; doxorubicin

Campos de Estudio

Financiación

Asociacion Espanola Contra el Cancer
Generalitat Valenciana (ACIF/2018/119)
INSTITUTO SALUD CARLOS III (CB16/12/00481)
INSTITUTO SALUD CARLOS III (PI18/01219)
INSTITUTO SALUD CARLOS III (PI21/01351)
Spanish Government - FEDER Funds (PI21/00142)

Proyectos y Estudios Clínicos

INCORPORACIÓN DE NUEVAS ÁREAS TEMÁTICAS Y NUEVOS GRUPOS AL CONSORCIO CIBER

Investigador Principal: ANA LLUCH HERNÁNDEZ

CB16/12/00481 . INSTITUTO SALUD CARLOS III

Caracterizacion y repercusion terapeutica de la ecologia de cancer de mama HER2 positivo

Investigador Principal: PILAR EROLES ASENSIO

PI18/01219 . INSTITUTO SALUD CARLOS III . 2019

Predicción de enfermedad residual después de la terapia neoadyuvante en cáncer de mama HER2 positivo e identificación de estrategias para superar la resistencia.

Investigador Principal: PILAR EROLES ASENSIO

PI21/01351 . INSTITUTO SALUD CARLOS III . 2022

Cita

Compartir