Perineural invasion is frequently observed in pancreatic cancers and they exhibit focal differentiation surrounding the peripheral nerves. Neighboring schwann cells lead to the differentiation of invasive tumor cells and the formation of the tubule-like structures. The nerve growth factors are responsible for this peri-neural invasion with differentiation?
The co-culture experiment in combination of schwann cells with pancreatic cancer cells in vitro leads to the enhanced migration potential as well as higher levels of differentiation molecule expression in a heterogeneous way. It is noteworthy that the co-culture system without cell-to-cell attachment cannot induce the same result, indicating the possibility that neither soluble growth factors nor exosomes containing micro-RNA cannot be the cause of the alteration of tumor cell phenotype.
Surely MMP is a likely candidate to promote the peri-neural invasion, but this is soluble in stromal fluids. Thus I do not think MMP can explain the cell-contact-dependent manner of peri-neural invasion and accompanied the focal differentiation of invasive tumor cells.
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