tretinoin and Rhabdomyosarcoma--Alveolar

We recently established a cell line derived from pleural effusion from a 13-year-old girl with primary alveolar rhabdomyosarcoma (RMS with a chromosomal translocation t[2;13]) in the breast tissue. The cell line was designated as HUMEMS. Cases of primary alveolar RMS swelling in the breast are extremely rare (about 0.2% of all RMSs). Therefore, the HUMEMS cell line is an important material for studying therapeutics for malignant tumors in children. The HUMEMS cell line we isolated consisted of two morphological subtypes. One type (SSN cells) is small in size and has a single nucleus. Another (LMN cells) is large in size and has two or more nuclei. Both SSN cells and LMN cells were immunohistochemically positive for desmin and slightly positive for myoglobin. Our data suggested LMN cells are well-differentiated SSN cells. Moreover, in some of the LMN cells, rapid cell contractions (1-5 times/10 sec) were observed. We investigated the anticancer drug susceptibility of the HUMEMS cell line with an oxygen electrode apparatus (Daikin, DOX-10, JPN) and effect of all-trans-retinoic acid (atRA) to the cell line. The atRA-treatment inhibited proliferation of the HUMEMS cells.

Topics: Adolescent; Breast Neoplasms; Cell Line, Tumor; Cell Nucleus; Desmin; Drug Screening Assays, Antitumor; Female; Humans; Immunohistochemistry; Myoglobin; Pleural Effusion, Malignant; Rhabdomyosarcoma, Alveolar; Tretinoin

Vascular endothelial growth factor (VEGF) is a potent signalling molecule that acts through two tyrosine kinase receptors, VEGFR1 and VEGFR2. The upregulation of VEGF and its receptors is important in tumour-associated angiogenesis; however, recent studies suggest that several tumour cells express VEGF receptors and may be influenced by autocrine VEGF signalling. Rhabdomyosarcoma (RMS) is the most common paediatric soft-tissue sarcoma, and is dependent on autocrine signalling for its growth. The alveolar subtype of RMS is often characterized by the presence of a PAX3-FKHR translocation, and when introduced into non-RMS cells, the resultant fusion protein induces expression of VEGFR1. In our study, we examined the expression of VEGF and its receptors in RMS, and autocrine effects of VEGF on cell growth. VEGF and receptor mRNA and protein were found to be expressed in RMS cells. Exogenous VEGF addition resulted in extracellular signal-regulated kinase-1/2 phosphorylation and cell proliferation, and both were reduced by VEGFR1 blockade. Growth was also slowed by VEGFR1 inhibitor alone. Treatment of RMS cells with all-trans-retinoic acid decreased VEGF secretion and slowed cell growth, which was rescued by VEGF. These data suggest that autocrine VEGF signalling likely influences RMS growth and its inhibition may be an effective treatment for RMS.

Topics: Autocrine Communication; Blotting, Western; Cell Count; Cell Culture Techniques; Cell Division; Cell Line, Tumor; Cell Proliferation; Cell Survival; Endothelium, Vascular; Fluorescent Antibody Technique, Indirect; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Phosphorylation; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; Rhabdomyosarcoma, Alveolar; Rhabdomyosarcoma, Embryonal; RNA, Messenger; Tretinoin; Umbilical Veins; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2