La Trobe
4.pdf (816.53 kB)

Secretome-based proteomics reveals sulindac-modulated proteins released from colon cancer cells

Download (816.53 kB)
journal contribution
posted on 13.08.2021, 01:37 by H Ji, David GreeningDavid Greening, EA Kapp, RL Moritz, Richard SimpsonRichard Simpson
Although experiments in rodents and human population-based studies have demonstrated the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac in colorectal cancer (CRC) prevention, a detailed knowledge of the underlying mechanism of action of this drug is limited. To better understand the chemopreventitive effects of sulindac, especially early sulindac-induced apoptotic events, we used the CRC cell line LIM1215 as an experimental model, focusing on proteins secreted into the LIM1215 culture medium-i.e., the secretome. This subproteome comprises both soluble-secreted proteins and exosomes (30-100 nm diameter membrane vesicles released by several cell types). Selected secretome proteins whose expression levels were dysregulated by 1 mM sulindac treatment over 16 h were analyzed using 2-D DIGE, cytokine array, Western blotting, and MS. Overall, 150 secreted proteins were identified, many of which are implicated in molecular and cellular functions such as cell proliferation, differentiation, adhesion, invasion, angiogenesis, metastasis, and apoptosis. Our secretome-based proteomic studies have identified several secreted modulators of sulindac-induced apoptosis action (e.g., Mac-2 binding protein, Alix, 14-3-3 isoforms, profilin-1, calumenin/Cab45 precursors, and the angiogenic/tumor growth factors interleukin 8 (IL-8) and growth related oncogene (GRO-α)) that are likely to improve our understanding of the chemopreventitive action of this NSAID in CRC. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Funding

This work was supported by the Australian National Health & Medical Research Council Program grant no. 280912 (RJ.S.) and a University of Melbourne Post-Graduate Student Scholarship (D.WG.).

History

Publication Date

14/05/2009

Journal

Proteomics - Clinical Applications

Volume

3

Issue

4

Pagination

(p. 433-451)

Publisher

WILEY-V C H VERLAG GMBH

ISSN

1862-8346

Rights Statement

The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.