Next Article in Journal
Detection of ER Stress in iPSC-Derived Neurons Carrying the p.N370S Mutation in the GBA1 Gene
Next Article in Special Issue
Beyond Triple-Negative: High Prevalence of Quadruple-Negative Breast Cancer in African Americans
Previous Article in Journal
Diagnosis of Glaucoma Based on Few-Shot Learning with Wide-Field Optical Coherence Tomography Angiography
Previous Article in Special Issue
Activation of MAP Kinase Pathway by Polyisoprenylated Cysteinyl Amide Inhibitors Causes Apoptosis and Disrupts Breast Cancer Cell Invasion
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Biomedicines
Volume 12
Issue 4
10.3390/biomedicines12040742
biomedicines-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Low-Density Lipoproteins Increase Proliferation, Invasion, and Chemoresistance via an Exosome Autocrine Mechanism in MDA-MB-231 Chemoresistant Cells

by
César Y. Castañeda-Sánchez
1,2,
Brenda Chimal-Vega
1,2,
Roberto León-Gutiérrez
1,2,
Adrián Ernesto Araiza-Robles
1,2,
Nicolás Serafín-Higuera
3,
Angel Pulido-Capiz
1,2,
Ignacio A. Rivero
4,
Raúl Díaz-Molina
1,2,
Manuel Alatorre-Meda
5,
Eustolia Rodríguez-Velázquez
6,7 and
Victor García-González
1,2,*
1
Departamento de Bioquímica, Facultad de Medicina Mexicali, Universidad Autónoma de Baja California, Mexicali 21000, Mexico
2
Laboratorio Multidisciplinario de Estudios Metabólicos y Cáncer, Universidad Autónoma de Baja California, Mexicali 21000, Mexico
3
Facultad de Odontología Mexicali, Universidad Autónoma de Baja California, Mexicali 21000, Mexico
4
Centro de Graduados e Investigación en Química, Tecnológico Nacional de México, Instituto Tecnológico de Tijuana, Tijuana 22510, Mexico
5
Centro de Graduados e Investigación en Química-Grupo de Biomateriales y Nanomedicina, CONAHCYT-Tecnológico Nacional de México, Instituto Tecnológico de Tijuana, Tijuana 22510, Mexico
6
Facultad de Odontología, Universidad Autónoma de Baja California, Tijuana 22390, Mexico
7
Centro de Graduados e Investigación en Química-Grupo de Biomateriales y Nanomedicina, Tecnológico Nacional de México, Instituto Tecnológico de Tijuana, Tijuana 22510, Mexico
*
Author to whom correspondence should be addressed.
Biomedicines 2024, 12(4), 742; https://doi.org/10.3390/biomedicines12040742
Submission received: 23 December 2023 / Revised: 1 March 2024 / Accepted: 7 March 2024 / Published: 27 March 2024
(This article belongs to the Special Issue Molecular Research of Triple-Negative Breast Cancer)
Browse Figures
Versions Notes

Abstract

Dyslipidemias involving high concentrations of low-density lipoproteins (LDLs) increase the risk of developing triple-negative breast cancer (TNBC), wherein cholesterol metabolism and protein translation initiation mechanisms have been linked with chemoresistance. Doxorubicin (Dox) treatment, a member of the anthracycline family, represents a typical therapeutic strategy; however, chemoresistance remains a significant challenge. Exosomes (Exs) secreted by tumoral cells have been implicated in cell communication pathways and chemoresistance mechanisms; the content of exosomes is an outcome of cellular cholesterol metabolism. We previously induced Dox resistance in TNBC cell models, characterizing a variant denominated as variant B cells. Our results suggest that LDL internalization in parental and chemoresistant variant B cells is associated with increased cell proliferation, migration, invasion, and spheroid growth. We identified the role of eIF4F translation initiation factor and the down-regulation of tumor suppressor gene PDCD4, an inhibitor of eIF4A, in chemoresistant variant B cells. In addition, the exomes secreted by variant B cells were characterized by the protein content, electronic microscopy, and cell internalization assays. Critically, exosomes purified from LDL-treated variant B cell promoted cell proliferation, migration, and an increment in lactate concentration. Our results suggest that an autocrine phenomenon induced by exosomes in chemoresistant cells may induce modifications on signaling mechanisms of the p53/Mdm2 axis and activation of p70 ribosomal protein kinase S6. Moreover, the specific down-regulated profile of chaperones Hsp90 and Hsp70 secretion inside the exosomes of the chemoresistant variant could be associated with this phenomenon. Therefore, autocrine activation mediated by exosomes and the effect of LDL internalization may influence changes in exosome chaperone content and modulate proliferative signaling pathways, increasing the aggressiveness of MDA-MB-231 chemoresistant cells.
Keywords: triple-negative breast cancer; chemoresistance; LDL; doxorubicin; exosomes; Hsp90; Hsp70 triple-negative breast cancer; chemoresistance; LDL; doxorubicin; exosomes; Hsp90; Hsp70

Share and Cite

MDPI and ACS Style

Castañeda-Sánchez, C.Y.; Chimal-Vega, B.; León-Gutiérrez, R.; Araiza-Robles, A.E.; Serafín-Higuera, N.; Pulido-Capiz, A.; Rivero, I.A.; Díaz-Molina, R.; Alatorre-Meda, M.; Rodríguez-Velázquez, E.; et al. Low-Density Lipoproteins Increase Proliferation, Invasion, and Chemoresistance via an Exosome Autocrine Mechanism in MDA-MB-231 Chemoresistant Cells. Biomedicines 2024, 12, 742. https://doi.org/10.3390/biomedicines12040742

AMA Style

Castañeda-Sánchez CY, Chimal-Vega B, León-Gutiérrez R, Araiza-Robles AE, Serafín-Higuera N, Pulido-Capiz A, Rivero IA, Díaz-Molina R, Alatorre-Meda M, Rodríguez-Velázquez E, et al. Low-Density Lipoproteins Increase Proliferation, Invasion, and Chemoresistance via an Exosome Autocrine Mechanism in MDA-MB-231 Chemoresistant Cells. Biomedicines. 2024; 12(4):742. https://doi.org/10.3390/biomedicines12040742

Chicago/Turabian Style

Castañeda-Sánchez, César Y., Brenda Chimal-Vega, Roberto León-Gutiérrez, Adrián Ernesto Araiza-Robles, Nicolás Serafín-Higuera, Angel Pulido-Capiz, Ignacio A. Rivero, Raúl Díaz-Molina, Manuel Alatorre-Meda, Eustolia Rodríguez-Velázquez, and et al. 2024. "Low-Density Lipoproteins Increase Proliferation, Invasion, and Chemoresistance via an Exosome Autocrine Mechanism in MDA-MB-231 Chemoresistant Cells" Biomedicines 12, no. 4: 742. https://doi.org/10.3390/biomedicines12040742

APA Style

Castañeda-Sánchez, C. Y., Chimal-Vega, B., León-Gutiérrez, R., Araiza-Robles, A. E., Serafín-Higuera, N., Pulido-Capiz, A., Rivero, I. A., Díaz-Molina, R., Alatorre-Meda, M., Rodríguez-Velázquez, E., & García-González, V. (2024). Low-Density Lipoproteins Increase Proliferation, Invasion, and Chemoresistance via an Exosome Autocrine Mechanism in MDA-MB-231 Chemoresistant Cells. Biomedicines, 12(4), 742. https://doi.org/10.3390/biomedicines12040742

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop