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Title: Tetraspanin 7 (TSPAN7) expression is upregulated in multiple myeloma patients and inhibits myeloma tumour development in vivo

Abstract

Background: Increased expression of the tetraspanin TSPAN7 has been observed in a number of cancers; however, it is unclear how TSPAN7 plays a role in cancer progression. Methods: We investigated the expression of TSPAN7 in the haematological malignancy multiple myleoma (MM) and assessed the consequences of TSPAN7 expression in the adhesion, migration and growth of MM plasma cells (PC) in vitro and in bone marrow (BM) homing and tumour growth in vivo. Finally, we characterised the association of TSPAN7 with cell surface partner molecules in vitro. Results: TSPAN7 was found to be highly expressed at the RNA and protein level in CD138{sup +} MM PC from approximately 50% of MM patients. TSPAN7 overexpression in the murine myeloma cell line 5TGM1 significantly reduced tumour burden in 5TGM1/KaLwRij mice 4 weeks after intravenous adminstration of 5TGM1 cells. While TSPAN7 overexpression did not affect cell proliferation in vitro, TSPAN7 increased 5TGM1 cell adhesion to BM stromal cells and transendothelial migration. In addition, TSPAN7 was found to associate with the molecular chaperone calnexin on the cell surface. Conclusion: These results suggest that elevated TSPAN7 may be associated with better outcomes for up to 50% of MM patients. - Highlights: • TSPAN7 expression is upregulatedmore » in newly-diagnosed patients with active multiple myeloma. • Overexpression of TSPAN7 inhibits myeloma tumour development in vivo. • TSPAN7 interacts with calnexin at the plasma membrane in a myeloma cell line.« less

Authors:
 [1];  [1];  [2];  [1];  [1];  [2];  [1];  [2];  [2];  [1];  [3];
  1. Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia)
  2. (Australia)
  3. Department of Haematology, SA Pathology, Adelaide 5000, SA (Australia)
Publication Date:
OSTI Identifier:
22462265
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 332; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BONE MARROW; CELL PROLIFERATION; DIAGNOSIS; FLUORESCENCE; IN VITRO; IN VIVO; LEUKEMIA; LIQUID COLUMN CHROMATOGRAPHY; MASS SPECTROSCOPY; MEMBRANES; MICE; MOLECULES; PATIENTS; PLASMA; PLASMA CELLS; PROTEINS; RNA

Citation Formats

Cheong, Chee Man, Chow, Annie W.S., Department of Haematology, SA Pathology, Adelaide 5000, SA, Fitter, Stephen, Hewett, Duncan R., School of Medicine, University of Adelaide, Adelaide 5005, SA, Martin, Sally K., Department of Haematology, SA Pathology, Adelaide 5000, SA, School of Medicine, University of Adelaide, Adelaide 5005, SA, Williams, Sharon A., To, L. Bik, and and others. Tetraspanin 7 (TSPAN7) expression is upregulated in multiple myeloma patients and inhibits myeloma tumour development in vivo. United States: N. p., 2015. Web. doi:10.1016/J.YEXCR.2015.01.006.
Cheong, Chee Man, Chow, Annie W.S., Department of Haematology, SA Pathology, Adelaide 5000, SA, Fitter, Stephen, Hewett, Duncan R., School of Medicine, University of Adelaide, Adelaide 5005, SA, Martin, Sally K., Department of Haematology, SA Pathology, Adelaide 5000, SA, School of Medicine, University of Adelaide, Adelaide 5005, SA, Williams, Sharon A., To, L. Bik, & and others. Tetraspanin 7 (TSPAN7) expression is upregulated in multiple myeloma patients and inhibits myeloma tumour development in vivo. United States. doi:10.1016/J.YEXCR.2015.01.006.
Cheong, Chee Man, Chow, Annie W.S., Department of Haematology, SA Pathology, Adelaide 5000, SA, Fitter, Stephen, Hewett, Duncan R., School of Medicine, University of Adelaide, Adelaide 5005, SA, Martin, Sally K., Department of Haematology, SA Pathology, Adelaide 5000, SA, School of Medicine, University of Adelaide, Adelaide 5005, SA, Williams, Sharon A., To, L. Bik, and and others. Sun . "Tetraspanin 7 (TSPAN7) expression is upregulated in multiple myeloma patients and inhibits myeloma tumour development in vivo". United States. doi:10.1016/J.YEXCR.2015.01.006.
@article{osti_22462265,
title = {Tetraspanin 7 (TSPAN7) expression is upregulated in multiple myeloma patients and inhibits myeloma tumour development in vivo},
author = {Cheong, Chee Man and Chow, Annie W.S. and Department of Haematology, SA Pathology, Adelaide 5000, SA and Fitter, Stephen and Hewett, Duncan R. and School of Medicine, University of Adelaide, Adelaide 5005, SA and Martin, Sally K. and Department of Haematology, SA Pathology, Adelaide 5000, SA and School of Medicine, University of Adelaide, Adelaide 5005, SA and Williams, Sharon A. and To, L. Bik and and others},
abstractNote = {Background: Increased expression of the tetraspanin TSPAN7 has been observed in a number of cancers; however, it is unclear how TSPAN7 plays a role in cancer progression. Methods: We investigated the expression of TSPAN7 in the haematological malignancy multiple myleoma (MM) and assessed the consequences of TSPAN7 expression in the adhesion, migration and growth of MM plasma cells (PC) in vitro and in bone marrow (BM) homing and tumour growth in vivo. Finally, we characterised the association of TSPAN7 with cell surface partner molecules in vitro. Results: TSPAN7 was found to be highly expressed at the RNA and protein level in CD138{sup +} MM PC from approximately 50% of MM patients. TSPAN7 overexpression in the murine myeloma cell line 5TGM1 significantly reduced tumour burden in 5TGM1/KaLwRij mice 4 weeks after intravenous adminstration of 5TGM1 cells. While TSPAN7 overexpression did not affect cell proliferation in vitro, TSPAN7 increased 5TGM1 cell adhesion to BM stromal cells and transendothelial migration. In addition, TSPAN7 was found to associate with the molecular chaperone calnexin on the cell surface. Conclusion: These results suggest that elevated TSPAN7 may be associated with better outcomes for up to 50% of MM patients. - Highlights: • TSPAN7 expression is upregulated in newly-diagnosed patients with active multiple myeloma. • Overexpression of TSPAN7 inhibits myeloma tumour development in vivo. • TSPAN7 interacts with calnexin at the plasma membrane in a myeloma cell line.},
doi = {10.1016/J.YEXCR.2015.01.006},
journal = {Experimental Cell Research},
number = 1,
volume = 332,
place = {United States},
year = {Sun Mar 01 00:00:00 EST 2015},
month = {Sun Mar 01 00:00:00 EST 2015}
}