Microenvironment is an active player in solid tumor biology. Tumor cells establish a functional and metabolic crosstalk with tumor cells favoring their survive and growth in a hostile environment. Such an interplay also favors tumor aggressiveness and spread.
Pheochromocytomas and paragangliomas (PPGLs) are neural crest-derived tumors showing the highest rate of malignancy when SDHB mutated.
Co-culturing the human neuroblastoma cell line SK-N-AS with fibroblasts, as representative of microenvironment, a reciprocal effect between the two type of cells changes their metabolic pattern as well as tumor cell growth and invasion potential. SDHB silencing increases these effects. When using a mouse metastatic pheochromocytoma cell line (MTT), a similar crosstalk with fibroblasts was observed, with minor differences in the metabolic consequences while the increase in tumor cell migration/invasion were confirmed and found further enhanced by SDHB silencing. These studies strongly support a role for the microenvironment in sustaining tumor growth and invasiveness. These effects are further enhanced in SDHB silenced cells. The comprehension of the factors that specifically increase the invasiveness of SDHB silenced cells might suggest potential therapeutic targets to block or slow the progression of SDHB related metastatic PPGLs.