Expression and roles of keratinocyte growth factor and its receptor in esophageal cancer cells

Abstract

Abstract. The keratinocyte growth factor receptor (KGFR), also known as FGFR2 IIIb, is mainly localized in epithelial cells and is activated by the keratinocyte growth factor (KGF) that is predominantly synthesized by mesenchymal cells. In this study, we examined the roles of KGFR and KGF in human esophageal cancer (EC). In noncancerous esophageal tissues, KGFR was localized in epithelial cells from the basal region of the epithelium to the lower one-third of the epithelium, and KGF was weakly localized in the basal to parabasal epithelial cells. On the other hand, Ki-67 was localized in the parabasal cells. In EC tissues, KGFR and KGF were expressed in cancer cells in 22 and 37 of 54 patients, respectively. The coexpression of KGFR and KGF in cancer cells was detected in 14 of 54 (26%) patients. Clinicopathologically, KGFR expression correlated with the well-differentiated cell type of EC (p<0.001), and KGF expression correlated with lymphatic invasion and lymph node metastasis (p=0.004 and 0.021, respectively). The coexpression of KGFR and KGF in cancer cells correlated with the well-differentiated cell type of EC (p=0.001). KGFR-positive, KGF-positive and KGFR/KGF coexpression patients tended to have shorter survival rates, but the survival rates were not statistically significantly different (p=0.44, 0.059 and 0.112, respectively). In human EC cell lines (TE-1, TE-8 and TE-11), KGFR mRNA was expressed but no KGF mRNA was detected. The KGFR mRNA level was highest in TE-1 cells, derived from well-differentiated SCC and lowest in TE-8 cells. KGFR was detected in the cancer cell lines by Western blot analysis. Recombinant human KGF significantly stimulated the growth of TE-8 and -11 cells, derived from moderately differentiated SCC, but had no effect on TE-1 cell growth. These results suggest that KGFR expression correlates with the differentiation of a normal esophageal epithelium and the well-differentiated cell type of EC. On the other hand, KGF may induce the growth of some EC cells in a paracrine manner and closely correlates with lymphatic invasion and lymph node metastasis.

Genetic Variations in MicroRNA-Related Genes Are Novel Susceptibility Loci for Esophageal Cancer Risk

“…There were 11 predicted targets for mir423 . Two of them, PABPC1 (41) and FGFR2 (42), were shown to be associated with the etiology or prognosis of esophageal cancer. Takashima et al (41) demonstrated that down-regulation of PABPC1 was associated with tumor progression, including increased tumor size, locally invasive tumors, and poor overall survival.…”

“…Takashima et al (41) demonstrated that down-regulation of PABPC1 was associated with tumor progression, including increased tumor size, locally invasive tumors, and poor overall survival. Yoshino et al (42) showed that over-expression of FGFR2 was highly correlated with well-differentiated esophageal cancer. Six HOX genes including HOXA5 , HOXA7 , HOXA9 , HOXB6 , HOXB7 , and HOXC8 , were among the predicted targets of mir196a-2 .…”

Keratinocyte growth factor receptor: a therapeutic target in solid cancer

“…The recombinant human KGF could enhance several parameters of cellular motility in estrogen receptor (ER)-positive breast cancer cell lines but not in ER-negative cell lines [39]. Yoshino et al investigated the role of KGFR and KGF in human esophageal cancer (EC) [40]. In EC tissues, KGFR and KGF were expressed in cancer cells in 22 and 37 of 54 patients, respectively.…”

“…Overexpression of KGFR can lead to mitogenesis and tumor progression in some cancer types [37][38][39][40][41].…”

Synthesis and in vivo evaluation of N-ethylamino-2-oxo-1,2-dihydro-quinoline-3-carboxamide for inhibition of intestinal tumorigenesis in APCMin/+ mice

“…3 In addition, over-expression of KGF and/or KGFR is associated with the progression of several types of cancers including colorectal cancers. 4–7 KGF/KGFR signaling via the ERK1/2 pathway often occurs early in the process of cancer cell initiation by enhancing cell proliferation and motility resulting in progression to a metastatic phenotype. 8 Colorectal cancers are thought to arise due to a series of histopathologic and molecular changes that transform normal colonic epithelial cells into colorectal carcinoma, with an adenomatous polyp as an intermediate step in this process.…”