Cancer microcell initiation and determination

BMC Cancer. 2021 Oct 8;21(1):1087. doi: 10.1186/s12885-021-08813-5.

Abstract

Background: Cancer remains one of the leading causes of death worldwide, despite the possibilities to detect early onset of the most common cancer types. The search for the optimal therapy is complicated by the cancer diversity within tumors and the unsynchronized development of cancerous cells. Therefore, it is necessary to characterize cancer cell populations after treatment has been applied, because cancer recurrence is not rare. In our research, we concentrated on small cancer cell subpopulation (microcells) that has a potential to be cancer resistance source. Previously made experiments has shown that these cells in small numbers form in specific circumstances after anticancer treatment.

Methods: In experiments described in this research, the anticancer agents' paclitaxel and doxorubicin were used to stimulate the induction of microcells in fibroblast, cervix adenocarcinoma, and melanoma cell lines. Mainly for the formation of microcells in melanoma cells. The drug-stimulated cells were then characterized in terms of their formation efficiency, morphology, and metabolic activity.

Results: We observed the development of cancer microcells and green fluorescent protein (GFP) transfection efficiency after stress. In the time-lapse experiment, we observed microcell formation through a renewal process and GFP expression in the microcells. Additionally, the microcells were viable after anticancer treatment, as indicated by the nicotinamide adenine dinucleotide hydrogen phosphate (NADPH) enzyme activity assay results. Taken together, these findings indicate that cancer microcells are viable and capable of resisting the stress induced by anticancer drugs, and these cells are prone to chemical substance uptake from the environment.

Conclusion: Microcells are not only common to a specific cancer type, but can be found in any tumor type. This study could help to understand cancer emergence and recurrence. The appearance of microcells in the studied cancer cell population could be an indicator of the individual anticancer therapy effectiveness and patient survival.

Keywords: Cell viability; Doxorubicin; Microcell; NADPH; Paclitaxel; SK-MEL-28; cancer; cancer resistance.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Antineoplastic Agents / pharmacology*
  • Cell Count
  • Cell Line, Tumor
  • Cell Nucleus / ultrastructure
  • Cell Self Renewal
  • Cell Survival / drug effects
  • DNA-Binding Proteins / metabolism
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm*
  • Endosomal Sorting Complexes Required for Transport / metabolism
  • Female
  • Fibroblasts / drug effects
  • Green Fluorescent Proteins / metabolism
  • HeLa Cells
  • Humans
  • Indicators and Reagents / pharmacokinetics
  • Melanoma / metabolism
  • Melanoma / pathology
  • Microscopy, Electron
  • NADP / metabolism
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Neoplasms / ultrastructure
  • Neutral Red / pharmacokinetics
  • Paclitaxel / pharmacology
  • Stress, Physiological
  • Time-Lapse Imaging
  • Transcription Factors / metabolism
  • Transfection
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Indicators and Reagents
  • Transcription Factors
  • Tsg101 protein
  • Green Fluorescent Proteins
  • Neutral Red
  • NADP
  • Doxorubicin
  • Paclitaxel