Enhancing effects of fibroblast growth factor on the proliferation of salivary gland carcinoma cells and salivary gland carcinogenesis

Abstract

The proliferation of mouse submandibular gland carcinoma YT-12 cells was stimulated by endothelial cell growth factor (ECGF)/bovine brain-derived acidic fibroblast growth factor (aFGF) and recombinant human aFGF. To determine whether aFGF was capable of modifying salivary gland carcinogenesis, the effect of brain-derived aFGF was examined in vivo. Mice in Groups 1 and 2 were injected with 9,10-dimethyl-1,2-benzanthracene (DMBA) into the left submandibular gland, and then Group 1 mice received bovine brain-derived aFGF and Group 2 mice received vehicle subcutaneously for 10 weeks. Group 3 and 4 mice received either bovine brain-derived aFGF or vehicle only. Sixteen weeks after the start of the experiment, the incidence of submandibular gland carcinomas in Group 1 was significantly greater than that in Group 2. Immunohistochemical study indicated that ducts in the normal submandibular glands and carcinomas showed positive staining with anti-aFGF antibody. Immunoblot and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the expression of aFGF in these tissues. FGF receptor (FGFR)-1 and FGFR-4 were detectable in the mouse submandibular glands and carcinomas. These findings suggest that bovine brain-derived aFGF stimulates the proliferation of submandibular gland carcinoma cells and promotes mouse submandibular gland carcinogenesis.

Study of growth factors and receptors in carcinoma ex pleomorphic adenoma

“…Several growth factors are involved in carcinoma initiation and progression including fibroblast growth factor (FGF), hepatocyte growth factor (HGF), epidermal growth factor (EGF), insulin‐like growth factor (IGF) and transforming growth factor β (TGFβ) (8–17). Growth factors and their receptors have been intensely studied in tumorigenesis of mammary, skin, prostate and bladder carcinomas (18–21), blood cancer (8, 22), neural astrocytoma (23), but rarely studied in salivary gland tumors (24–27).…”

Keratinocyte Growth Factor-1 Protects Radioiodine-Induced Salivary Gland Dysfunction in Mice

“…Growth factors have been used to regenerate SG cells exposed to radiation, [ 21 , 22 , 23 ] but some growth factors are of limited clinical because of adverse effects, which include carcinogenesis and restriction of cancer therapy [ 24 , 25 ]. In murine xenograft models of head and neck carcinoma, subcutaneously injected KGF-1 did influence tumor growth of chemotherapeutic efficacy [ 10 ].…”

Non‐mitogenic acidic fibroblast growth factor reduces intestinal dysfunction induced by ischemia and reperfusion injury in rats

“…[1][2][3][4][5] Acidic FGF, a 17-kDa single-chain polypeptide, is an extremely potent inducer of DNA synthesis in a variety of cell types, and also has chemotactic and mitogenic activity. In the last few years, growing evidence from both animal experiments and clinical observations indicates that aFGF plays a protective role in I/R injury, [2][3][4] but the mitogenic activity of aFGF was found to contribute to several human pathologies, such as tumorigenesis and metastasis, 1,6,7 so the applications of wild-type aFGF have been limited. To decrease the potential side-effects of aFGF caused by its broad-spectrum mitogenic activity, a shortened non- mitogenic form of aFGF was constructed genetically that does not induce cell division, triggers the mitogenic activity, but retains the neuromodulatory, vasoactive, cardioprotective and neuroprotective properties of the native full-length wild-type aFGF.…”