transforming-growth-factor-alpha and Lymphoma--Large-B-Cell--Diffuse

Recent prospective studies have shown that dysregulation of the immune system may precede the development of B-cell lymphomas (BCL) in immunocompetent individuals. However, to date, the studies were restricted to a few immune markers, which were considered separately. Using a nested case-control study within two European prospective cohorts, we measured plasma levels of 28 immune markers in samples collected a median of 6 years before diagnosis (range 2.01-15.97) in 268 incident cases of BCL (including multiple myeloma [MM]) and matched controls. Linear mixed models and partial least square analyses were used to analyze the association between levels of immune marker and the incidence of BCL and its main histological subtypes and to investigate potential biomarkers predictive of the time to diagnosis. Linear mixed model analyses identified associations linking lower levels of fibroblast growth factor-2 (FGF-2 p = 7.2 × 10

Topics: Adult; Aged; Biomarkers; Case-Control Studies; Chemokine CCL7; Chemokine CX3CL1; Europe; Female; Fibroblast Growth Factor 2; Follow-Up Studies; Humans; Incidence; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Multiple Myeloma; Multivariate Analysis; Prognosis; Prospective Studies; Transforming Growth Factor alpha; Vascular Endothelial Growth Factor A

We have previously demonstrated that human promyelocytic HL-60 cells express transforming growth factor-alpha (TGF-alpha) during granulocytic differentiation. The present experiments were carried out in order to determine whether cells differentiated towards monocytes/macrophages will analogously express the TGF-alpha proto-oncogene product. HL-60 cells were induced to differentiate with 1 microM 1,alpha 25-dihydroxycholecalciferol (vitamin D3), and the human monocytoid cell line, U-937, was induced with 1 microM retinoic acid (RA), 0.1 microM vitamin D3, or 0.16 microM phorbol-12-myristate-13-acetate (PMA), ie experimental protocols known to induce monocyte/macrophage differentiation in these cells. In HL-60 cells, lacking constitutive TGF-alpha mRNA, vitamin D3 caused expression of the TGF-alpha gene and protein as demonstrated by Northern blot analysis and enzyme-linked immunoabsorbant assay (ELISA). In U-937 cells, showing constitutive TGF-alpha expression, RA but not vitamin D3 or PMA, caused marked increase in TGF-alpha mRNA (approximately 5-fold) and protein (approximately 3-fold) levels. In both cell lines the increase in TGF-alpha mRNA was evident within 24 h and continued throughout the observation period. Thus, it is established that differentiation of human leukemia cells towards monocytes/macrophages may be accompanied by TGF-alpha gene and protein expression in vitro. This is in conformity with the observed ability of mature activated macrophages to produce TGF-alpha.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Calcitriol; Cell Differentiation; Gene Expression; Humans; In Vitro Techniques; Integrin alphaXbeta2; Leukemia, Promyelocytic, Acute; Lipopolysaccharide Receptors; Lymphoma, Large B-Cell, Diffuse; Monocytes; Proto-Oncogene Mas; RNA, Messenger; RNA, Neoplasm; Time Factors; Transforming Growth Factor alpha; Tretinoin