Paralleling these observations, real-time PCR of Ccn1-deficient mouse fibroblasts and skin revealed that loss of CCN1 expression resulted in decreased mRNA expression of Mmp-9 (Fig. 7C and D; in cells, 0.870 ± 0.37 vs. 0.259 ± 0.139; in tissue 1.26 ± 0.109 vs. 0.757 ± 0.107), a gene whose expression is associated with acquisition of anti-PD1 resistance in melanoma (59–61). Here, MMP9 is linked to melanoma.