To define the matrix composition and architecture of canine flexor tendon, and to correlate tissue structure with applied mechanical loading, five anatomical regions of flexor tendon were studied. Histologically, two prominent fibrocartilaginous areas were observed on concave aspects of the tendon. The location of the major fibrocartilaginous area at the metacarpophalangeal joint correlated well with the region predicted by biomechanical modeling to be under greatest compressive loads during standing and claw movement. Comparative biochemical analysis showed an elevated water content, a five-fold higher hexuronic acid content, and a larger hydroxylysine/hydroxyproline ratio in this region relative to that for more tendinous areas. The major glycosaminoglycan component of fibrocartilaginous areas was chondroitin sulfate, whereas in other areas dermatan sulfate and hyaluronic acid dominated. Cell density and DNA analyses indicated a slightly higher cellularity for fibrocartilaginous areas and the region of vinculum insertion. These data document the existence of discrete areas of specialization within the flexor tendon that appear to be an adaptation to nutritional and mechanical factors.

Hepatoma-derived growth factor (HDGF) is highly expressed in tumor cells, and stimulates their proliferation. In the present study, we investigated the role of HDGF in tumorigenesis and elucidated the mechanism of action. Stable transfectants of NIH3T3 cells overexpressing HDGF did not show significant anchorage-independent growth in soft agar assay. However, these stable transfectants overexpressing HDGF generated sarcomatous tumors in nude mice. These tumors were red-colored macroscopically, and histologically showed a rich vascularity. Immunohistochemical analysis using CD31 antibody showed new vessel formation. Recombinant HDGF stimulated proliferation of human umbilical vein endothelial cells in a dose-dependent manner, and stimulated tubule formation. ncogenesis is induced by genetic alterations of various proteins involved in the cell cycle and cellular proliferation, especially by up-regulation of oncogenic genes and/or down-regulation of tumor suppressor genes. Overexpression of growth factors, receptors for growth factors, proteins related to signal transduction from the respective receptors and positive transcriptional regulatory factors, and suppressed expression of growth-inhibitory genes, including negative signal transducers and transcriptional regulatory factors, have all been associated with tumor formation in nude mice. [1][2][3][4][5][6][7][8][9] Hepatoma-derived growth factor (HDGF) is a heparin-binding protein purified from the conditioned media of Huh-7 hepatoma cells, which proliferate autonomously in a serum-free chemically defined medium.10, 11) HDGF contains a well-conserved N-terminal amino acid sequence, which is called the hath (homologous to amino terminus of HDGF) region. 11,12) HDGF is translocated to the nucleus via nuclear localization signals and its nuclear translocation is essential for induction of cell growth activity. 13,14) It is highly expressed in fetal tissues and may be involved in development of organs, including the cardiovascular system, kidney and liver. [15][16][17][18] HDGF has mitogenic activity for some hepatocellular carcinoma (HCC) cells, in addition to fibroblasts, endothelial cells, vascular smooth muscle cells and fetal hepatocytes. 10,11,13,15,16,18,19) It is abundantly expressed in tumor cell lines, and HDGF antisense oligonucleotides suppress the proliferation of hepatoma cells expressing HDGF endogenously. 19) In human and murine models of HCC, HDGF expression increases at an early stage, even before tumor formation. Furthermore, HDGF is more abundantly expressed in HCC than in adjacent non-tumor liver tissues.20) HDGF is a unique nuclear/growth factor, possibly playing an important role in the development and progression of cancer cells.Increasing evidence suggests that HDGF might be implicated in tumorigenesis. However, whether HDGF really induces transformation of cells and tumor formation in vivo is not known. Therefore, we established stable cell lines overexpressing HDGF from NIH3T3 fibroblasts by transfection, and investigated their oncogenic p...

These findings suggest the potential utility of HDGF immunohistochemistry in determining the prognosis of HCC.

Purpose: Hepatoma-derived growth factor (HDGF) is a nucleus-targeted growth factor playing an important role in the development and progression of cancers. This study investigated the correlation of HDGF expression and prognosis in patients with pancreatic ductal carcinoma. Patients and Methods: HDGF expression in pancreatic cancer cell lines was analyzed by Western blotting. HDGF expression was analyzed by immunohistochemistry for 50 patients with primary ductal carcinoma of the pancreas (33 male and 17 female) ranging in age from 48 to 80 years (median, 65 years) receiving surgical treatment. Cancer cells showing stronger staining than the noncancerous ducts were regarded as positive. Cases showing positive staining in <90% and >90% of tumor cells were regarded as HDGF labeling index (LI) levels 1and 2, respectively. HDGF LI was determined separately for the nucleus and the cytoplasm. Results: Western blotting showed HDGF expression in pancreatic cancer cells similar to that of hepatic cell lines.Twenty-three (46%) and 27 (54%) cases and 22 (44%) and 28 (56%) cases showed HDGF LI levels 1 and 2 for the nucleus and the cytoplasm, respectively. Patients with nuclear HDGF LI level 1 showed a significantly better 5-year survival rate (37.0%) than those with level 2 (6.8%; P = 0.023). No significant difference was observed in the cytoplasmic HDGF LI classification. Multivariate analysis revealed nuclear HDGF LI to be an independent prognosticator. Conclusions: These findings suggest that HDGF could be a novel prognostic factor for pancreatic ductal carcinoma.

The present findings suggest that HDGF plays an important role in the development or progression of HCC in humans and rodents.