Expression of teratocarcinoma-derived growth factor-1 (TDGF-1) in testis germ cell tumors and its effects on growth and differentiation of embryonal carcinoma cell line NTERA2/D1.
The teratocarcinoma-derived growth factor-1 (TDGF-1) gene codes for a 188-aminoacid glycoprotein that shares structural homology with the epidermal growth factor (EGF) family of growth factors. TDGF-1 is highly expressed in the undifferentiated embryonal carcinoma stem cell line NTERA2 clone D1 (NT2/D1) and its expression is downregulated in response to differentiating agents such as retinoic acid (RA) and hexamethylen-bisacetamide (HMBA). To assess the role of TDGF-1 in the onset and/or progression of human germ cell tumors, we analysed TDGF-1 expression by Northern blot and immunostaining in a panel of 59 human germ cell tumors of different histological origins. We show that TDGF-1 expression is markedly elevated in a subset of human testicular germ cell tumors as compared to normal testes. TDGF-1 overexpression occurs in about 100% of tumors with non-seminomatous phenotype, such as embryonal carcinomas and malignant undifferentiated teratocarcinomas. To address the questions of how TDGF-1 (previously called CRIPTO) may affect the growth and/or the differentiation of embryonal carcinoma cells, we have characterized the effects of exogenous recombinant TDGF-1 protein on the proliferation rate and differentiation 'potential of NT2/D1. Exogenous TDGF-1 protein stimulated DNA synthesis and cell proliferation in both undifferentiated and differentiated NT2/D1 cells. However, TDGF-1 protein treatment was unable to block differentiation induced by both RA and HMBA. These results suggest that TDGF-1 growth factor may represent an autocrine growth factor that may be involved in the process of development of testicular neoplasms.
Baldassarre
G
G
International Institute of Genetics and Biophysics, CNR, Naples, Italy.
Romano
A
A
Armenante
F
F
Rambaldi
M
M
Paoletti
I
I
Sandomenico
C
C
Pepe
S
S
Staibano
S
S
Salvatore
G
G
De Rosa
G
G
Persico
M G
MG
Viglietto
G
G
D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D015152:Blotting, Northern; D018236:Carcinoma, Embryonal / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004815:Epidermal Growth Factor; D058851:GPI-Linked Proteins; D015870:Gene Expression / Q000187:drug effects; D018237:Germinoma / Q000378:metabolism*; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D018243:Teratocarcinoma / Q000378:metabolism; D013736:Testicular Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; C070636:TDGF1 protein, human; D004815:Epidermal Growth Factor