Taken together, the tumor-suppressing effect of Bmp, particularly in vivo where tumor cells still express Shh (with 5’-azacitidine treatment) while the stromal Hh response is suppressed (using Col1a2CreER;Smoflox/flox and Col1a2CreER;Gli2flox/flox mice), supports a potential scenario of an increased reciprocal tumor-stromal signal feedback loop in which hypomethylation-induced Shh secretion by tumor cells activates the Hh response in bladder stroma, resulting in stromal expression of Bmps, which in turn signal back to tumor cells to impede their growth. This evidence concerns the gene CLN5 and neoplasm.