Increased secretory leukocyte protease inhibitor (SLPI) production by highly metastatic mouse breast cancer cells

The precise molecular mechanisms enabling cancer cells to metastasize from the primary tumor to different tissue locations are still largely unknown. Secretion of some proteins by metastatic cells could facilitate metastasis formation. The comparison of secreted proteins from cancer cells with diffe...

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Bibliographic Details
Published in:PloS one 2014-08, Vol.9 (8), p.e104223
Main Authors: Sayers, Kevin T, Brooks, Alan D, Sayers, Thomas J, Chertov, Oleg
Format: Article
Language:English
Subjects:
Animals
Biology and Life Sciences
Biomedical research
Breast cancer
Cancer
Cell culture
Cell Line, Tumor
Chromatography
Conditioning
DNA microarrays
Female
Gene expression
Gene Expression Regulation, Neoplastic
Growth factors
Laboratories
Leukocytes
Lysates
Mammary Neoplasms, Experimental - genetics
Mammary Neoplasms, Experimental - metabolism
Mammary Neoplasms, Experimental - pathology
Mass spectrometry
Medical research
Medicine and Health Sciences
Metastases
Metastasis
Mice
Molecular modelling
Neoplasm Metastasis
Ovarian cancer
Polymerase chain reaction
Protease
Protease inhibitors
Proteinase inhibitors
Proteins
Proteomics
Scientific imaging
Secretory Leukocyte Peptidase Inhibitor - biosynthesis
Secretory Leukocyte Peptidase Inhibitor - genetics
Secretory Leukocyte Peptidase Inhibitor - metabolism
Tumors
Western blotting
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Summary:The precise molecular mechanisms enabling cancer cells to metastasize from the primary tumor to different tissue locations are still largely unknown. Secretion of some proteins by metastatic cells could facilitate metastasis formation. The comparison of secreted proteins from cancer cells with different metastatic capabilities in vivo might provide insight into proteins involved in the metastatic process. Comparison of the secreted proteins from the mouse breast cancer cell line 4T1 and its highly metastatic 4T1.2 clone revealed a prominent differentially secreted protein which was identified as SLPI (secretory leukocyte protease inhibitor). Western blotting indicated higher levels of the protein in both conditioned media and whole cell lysates of 4T1.2 cells. Additionally higher levels of SLPI were also observed in 4T1.2 breast tumors in vivo following immunohistochemical staining. A comparison of SLPI mRNA levels by gene profiling using microarrays and RT-PCR did not detect major differences in SLPI gene expression between the 4T1 and 4T1.2 cells indicating that SLPI secretion is regulated at the protein level. Our results demonstrate that secretion of SLPI is drastically increased in highly metastatic cells, suggesting a possible role for SLPI in enhancing the metastatic behavior of breast cancer cell line 4T1.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0104223