Yeh et al. BMC Cancer 2011, 11:139 http://www.biomedcentral.com/1471-2407/11/139 Page 9 of 12 c-Met AXL PDGFR Figure 6 Co-expression of c-Met, Axl and PDGFR-a in a human bladder cancer specimen. Representative results of co-expression of c-Met, Axl and PDGFR-a in three serial sections of a human bladder cancer specimen. The three sections were incubated with anti-c-Met, anti-Axl or anti-PDGFR-a antibody, respectively (200X). The arrow indicates the specific expression of receptor protein around the membrane of the cancer cells. Table 2 Correlation of c-Met, Axl, and PDGFR-a protein expression with clinicopathologic parameters of patients with locally advanced and metastatic bladder cancers Expression pattern Grade T status* Multiple Node (+) c-Met 0.561 Axl 0.409 PDGFR-a 0.344 c-Met & Axl 0.140 c-Met & PDGFR-a 0.184 Axl & PDGFR-a 0.439 c-Met & Axl & PDGFR- 0.595 a 0.904 0.105 0.470 0.070 0.686 0.585 0.377 0.727 0.795 0.718 0.277 0.957 0.762 0.346 0.321 0.300 0.049† 0.061 0.802 0.369 0.281 *Statistical analysis was performed between stage pT2 (21), pT3 (27) and stage pT4 (17), according to TNM (2002) classification criteria. † p value less than 0.05. Survival 0.009† 0.789 0.027† 0.031† 0.011† 0.049† 0.008† suppression of Sp1, Axl and PDGFR-a by c-Met siRNA supports our speculation (Additional file 2). It has been reported that HGF is expressed in fibro- blast-like cells, smooth muscle cells, and endothelial cells of the bladder [46]. Expression of c-Met on the cancer cell surface thus may enable the paracrine activa- tion in vivo, irrespective of their capability to synthesize HGF. The correlation of co-expression of two or three of the RTKs with patient survival supports the “invasive growth” program in carcinomas with multiple RTK over-expression [13,15,47]. The prognostic significance of c-Met, whether alone or co-expressed with Axl/ PDGFR-a, supports the clinical relevance of c-Met- directed therapy (e.g. PHA665752) for human bladder cancer. Since the importance of co-targeting therapy for human bladder cancer having co-expressed RTKs has been demonstrated [15,47], a prospective study is