Evidence of lateral transmission of aggressive features between different types of breast cancer cells

Int J Oncol. 2017 Nov;51(5):1482-1496. doi: 10.3892/ijo.2017.4128. Epub 2017 Sep 19.

Abstract

Breast cancer (BrC) is a major public health problem worldwide. The intra-tumoral heterogeneity and tumor cell plasticity importantly contribute to disease progression and treatment failure. However, the dynamic interactions between different tumor clones, as well as their contribution to tumor aggressiveness are still poorly understood. In this study, we provide evidence of a lateral transmission of aggressive features between aggressive and non-aggressive tumor cells, consisting of gain of expression of cancer stem cell markers, increased expression of CXCL12 receptors CXCR4 and CXCR7 and increased invasiveness in response to CXCL12, which correlated with high levels of secretion of pro-inflammatory mediators G-CSF, GM-CSF, MCP-1, IL-8 and metalloproteinases 1 and 2 by the aggressive cells. Noteworthy, we found no evidence of a TGF-β participation in the inducible-invasive phenotype. Altogether, our results provide evidence of communication between tumor cells with different potentials for aggressiveness, which could influence intra-tumoral population dynamics promoting the emergence of clones with novel functions. Understanding these interactions will provide better targets for diagnosis, prognosis and therapeutic strategies.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Lineage / genetics
  • Cell Movement
  • Cell Proliferation / genetics
  • Chemokine CXCL12 / genetics
  • Clonal Evolution / genetics*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Heterogeneity*
  • Humans
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Receptors, CXCR / genetics
  • Receptors, CXCR4 / genetics
  • Signal Transduction
  • Transforming Growth Factor beta / genetics

Substances

  • ACKR3 protein, human
  • Biomarkers, Tumor
  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Receptors, CXCR
  • Receptors, CXCR4
  • Transforming Growth Factor beta