Role of tumor cell surface lysosome-associated membrane protein-1 (LAMP1) and its associated carbohydrates in lung metastasis

Agarwal, Akhil Kumar, Srinivasan, Nithya, Godbole, Rashmi, More, Shyam K, Budnar, Srikanth, Gude, Rajiv P and Kalraiya, Rajiv D (2015) Role of tumor cell surface lysosome-associated membrane protein-1 (LAMP1) and its associated carbohydrates in lung metastasis. Journal of Cancer Research and Clinical Oncology, 141 9: 1563-1574. doi:10.1007/s00432-015-1917-2


Author Agarwal, Akhil Kumar
Srinivasan, Nithya
Godbole, Rashmi
More, Shyam K
Budnar, Srikanth
Gude, Rajiv P
Kalraiya, Rajiv D
Title Role of tumor cell surface lysosome-associated membrane protein-1 (LAMP1) and its associated carbohydrates in lung metastasis
Journal name Journal of Cancer Research and Clinical Oncology   Check publisher's open access policy
ISSN 1432-1335
0171-5216
Publication date 2015-01-23
Year available 2015
Sub-type Article (original research)
DOI 10.1007/s00432-015-1917-2
Volume 141
Issue 9
Start page 1563
End page 1574
Total pages 12
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Formatted abstract
Purpose

Expression of lysosome-associated membrane protein-1 (LAMP1) on the surface correlates with metastatic potential of B16 melanoma cells. Downregulation of their expression in high metastatic (B16F10) cells reduced their surface expression and metastatic potential. Present investigations explore if overexpression of LAMP1 on the surface of low metastatic (B16F1) cells augment their metastatic ability, and if so, how?.

Methods

B16F1 cells were transduced with lentiviral vector carrying mutant-LAMP1 (Y386A) (mutLAMP1). Surface expression of LAMP1 and carbohydrates was analyzed by flow cytometry, immunofluorescence and/or immunoprecipitation and Western blotting. Cell spreading and motility were assessed on components of extracellular matrix (ECM) (fibronectin) and basement membrane (BM) (matrigel), and galectin-3-coated coverslips/plates. Metastatic potential was assessed using experimental metastasis assay.

Results

Pre-incubation with anti-LAMP1 antibodies significantly reduced lung metastasis of B16F10 cells. Overexpression of mutLAMP1 significantly increased its surface expression on B16F1 cells, resulting in increased cellular spreading and motility on fibronectin and matrigel. LAMP1 is the major carrier of poly-N-acetyllactosamine (polyLacNAc) on B16F10 cells. However, significantly higher expression of mutLAMP1 had no effect on galectin-3 binding on cell surface or on spreading or motility of cells on galectin-3-coated coverslips/plates. These cells also failed to show any gain in metastatic ability. This could be because LAMP1 from these cells carried significantly lower levels of polyLacNAc in comparison with B16F10 cells.

Conclusions

PolyLacNAc on B16F10 cells and galectin-3 on lungs are the major participants in melanoma metastasis. Although surface LAMP1 promotes interactions with organ ECM and BM, carbohydrates on LAMP1 play a decisive role in dictating lung metastasis.
Keyword Cell surface LAMP1
Organ-specific metastasis
β1,6 branched N-oligosaccharides
Poly-N-acetyllactosamine
Galectin-3
Motility
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
 
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