Effects of cell-cell crosstalk on gene expression patterns in a cell model of renal cell carcinoma lung metastasis

Abstract

The median survival rate of patients with metastatic renal carcinoma is approximately 10 to 12 months, with up to 50% of patients developing metastases in the lung parenchyma. The molecular basis for metastatic development remains unclear. In the present study, we used renal cell carcinoma (RCC) cells and bronchial epithelial cells, representing metastasis target organ cells, conditioned medium and co-culture models to identify specific gene expression changes responsible for cancer cell viability in a metastatic microenvironment. RCC cell proliferation and migration increased when the culture was supplemented with conditioned medium from lung fibroblasts or pleural epithelial cells. Healthy epithelial cells were, in turn, also stimulated with conditioned medium from RCC cell lines. The mitogen-activated protein kinase (MAPK), interleukin (IL)-6, and phosphatidylinositol 4,5-bisphosphate (PIP2) signaling pathways were identified as deregulated upon cell-cell interaction. Thus, cell-cell communication may contribute to the development of the metastatic niche. The identified deregulated signaling pathways may be considered as potential therapeutic targets in metastatic renal carcinoma.

Metastatic Tumor Burden and Loci as Predictors of First Line Sunitinib Treatment Efficacy in Patients with Renal Cell Carcinoma

“…Whole genome studies, microarray or next generation sequencing analysis, as well as fluorescent and bioluminescent imaging, may reveal how RCC subtypes differ not only in primary tumor characteristics but also in their metastatic behavior, in particular lung- or abdomen-homing characteristics or bone-seeking phenotype. Understanding the physiological link between the deregulation of specific genes and homing of certain metastases may impact treatment of RCC patients in the future 17,43 .…”

“…In the current state of knowledge, clinicians still lack the ability to predict to which category each patient will belong (fast, slow, or medium-progressors) but for long time it has been suggested that general tumor and metastatic burden might be one of the factors influencing the outcome 11–13 . Despite many advances in understanding RCC biology 14–17 , there is still a great deal of information to be discovered regarding the behavior of mRCC treated with VEGF-inhibiting agents both in molecular and clinical analyses 18,19 . Overall, measuring the size of tumors remains the simplest way to estimate the severity of disease and possibly predict response/progression on treatment in routine clinical practice world-wide.…”

Exploring cell-specific miRNA regulation with single-cell miRNA-mRNA co-sequencing data

“…The cell–cell crosstalk is an indirect cell–cell communication and plays an important role in biological systems. For instance, cell–cell crosstalk can influence gene expression patterns [ 35 ], and involve in the development and regeneration of the respiratory system as well [ 36 ]. For each cell–cell pair, a higher similarity means sharing more number of miRNA-mRNA interactions or hub miRNAs between two cells.…”

Exploring cell-specific miRNA regulation with single-cell miRNA-mRNA co-sequencing data

“…The cell-cell crosstalk is an indirect cell-cell communication and plays an important role in biological systems. For instance, cell-cell crosstalk can influence gene expression patterns [33], and involve in the development and regeneration of the respiratory system as well [34]. For each cell-cell pair, a higher similarity means sharing more number of miRNA-mRNA interactions or hub miRNAs between two cells.…”