Effects of polyclonal activators on cell differentiation and cytokine production of cultured invasive breast carcinoma of no special type, their association with tumour histopathological parameters and lymph node metastasis

Autor: A I Autenshlyus, V. A. Vavilin, Nikolay Varaksin, Vyacheslav V. Lyakhovich, Igor Marinkin, Elena Mikhailova, Sergey Arkhipov
Rok vydání: 2020
Předmět:
Adult
Lipopolysaccharides
0301 basic medicine
polyclonal activators
Lipopolysaccharide
Cellular differentiation
medicine.medical_treatment
Immunology
Breast Neoplasms
tumour cells
Metastasis
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Differentiation therapy
invasive breast carcinoma of no special type
Antineoplastic Combined Chemotherapy Protocols
Biopsy
Concanavalin A
medicine
Humans
metastasis
Immunology and Allergy
Neoplasm Invasiveness
Original Research Article
Phytohemagglutinins
Aged
Phytohaemagglutinin
Pharmacology
biology
medicine.diagnostic_test
business.industry
Carcinoma
Cell Differentiation
differentiation
Middle Aged
medicine.disease
cytokines
030104 developmental biology
Cytokine
chemistry
Polyclonal antibodies
Lymphatic Metastasis
030220 oncology & carcinogenesis
biology.protein
Cancer research
Female
business
Signal Transduction
Zdroj: International Journal of Immunopathology and Pharmacology
ISSN: 2058-7384
Popis: Currently, a number of promising strategies and approaches to cancer treatment include differentiation therapy. However, theoretical and methodological foundations of this field are not yet well developed. The objective of this study was to determine the effects of a mixture of polyclonal activators (PAs; phytohaemagglutinin, concanavalin A and lipopolysaccharide) on cytokine production by biopsy samples of invasive breast carcinoma of no special type (IBC-NST) having various differentiation abilities and metastatic potentials as well as on differentiation status of the IBC-NST biopsy samples. We used ELISAs to investigate spontaneous and PA-stimulated cytokine production in the IBC-NST biopsy samples; from these data, we calculated a cytokine production stimulation index (SIPA). The effect of PAs on tumour cell differentiation was determined via a differentiation stimulation index (DSI). DSI was found to vary within the range 1.0–5.0. After treatment with PAs, in the IBC-NST biopsy samples of group I (DSI 1.25), the production of IL-6, IL-1β, IL-1Ra, TNF-α, G-CSF and GM-CSF significantly increased, while the production of VEGF-A decreased. Receiver operating characteristic (ROC) analysis of SIPA revealed that increased production of IL-18 in the IBC-NST biopsy samples after exposure to PAs may block the PA-driven, cytokine-mediated differentiation of moderately differentiated into highly differentiated tumour cells. The ROC analysis also uncovered an association between the responses of tumour cells to PAs and lymph node metastasis observed in the patients. The findings suggest that there is a need for research aimed at finding new drugs for differentiating cancer therapy and at searching for targeted inducers of cytokine production or specific suppressors of their induction.
Databáze: OpenAIRE