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Anticancer Drugs Cause Release of Exosomes with Heat Shock Proteins from Human Hepatocellular Carcinoma Cells That Elicit Effective Natural Killer Cell Antitumor Responses in Vitro

Lv, Li-Hong, Wan, Yun-Le, Lin, Yan, Zhang, Wei, Yang, Mei, Li, Guo-Lin, Lin, Hao-Ming, Shang, Chang-Zhen, Chen, Ya-Jin, Min, Jun·2012·Journal of Biological Chemistry
DOI 10.1074/jbc.m112.340588
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FIGURE1 ChemosensitivityofHepG2andPLC/PRF/5cellstoanticancerdrugs. Dose-responsecurvesfor HepG2andPLC/PRF/5cellsfollowingcontinuous 72-h exposure to anticancer drugs at various concentrations using the MTT assay are depicted. For each single anticancer drug, chemosensitivity was determined to be sensitive (100% TDC > 90% and 50% TDC > 70%) or resistant (100% TDC < 70% and 50% TDC < 50%). HepG2 and PLC/PRF/5 cells showed significantly higher sensitivity to paclitaxel and etoposide compared with resistance to irinotecan hydrochloride, carboplatin, and mitomycin ( p < 0.05). Data shown are representative of nine independent experiments for each drug and each cell line with similar results.
FIGURE1 ChemosensitivityofHepG2andPLC/PRF/5cellstoanticancerdrugs. Dose-responsecurvesfor HepG2andPLC/PRF/5cellsfollowingcontinuous 72-h exposure to anticancer drugs at various concentrations using the MTT assay are depicted. For each single anticancer drug, chemosensitivity was determined to be sensitive (100% TDC > 90% and 50% TDC > 70%) or resistant (100% TDC < 70% and 50% TDC < 50%). HepG2 and PLC/PRF/5 cells showed significantly higher sensitivity to paclitaxel and etoposide compared with resistance to irinotecan hydrochloride, carboplatin, and mitomycin ( p < 0.05). Data shown are representative of nine independent experiments for each drug and each cell line with similar results.CC-BY · From the PDF
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FIGURE 3 Identification and characterization of exosomes secreted by HepG2cells under basal conditions. Exosomes were isolated by sequential centrifugations from supernatants of HepG2 cells under basal conditions. Shown is measurement of purified exosomal pellet by negative staining, showing a pure population with typical exosomal morphology ( A ), and Western blotting for the exosomal marker, tetraspan protein CD63 ( B ).
FIGURE 3 Identification and characterization of exosomes secreted by HepG2cells under basal conditions. Exosomes were isolated by sequential centrifugations from supernatants of HepG2 cells under basal conditions. Shown is measurement of purified exosomal pellet by negative staining, showing a pure population with typical exosomal morphology ( A ), and Western blotting for the exosomal marker, tetraspan protein CD63 ( B ).CC-BY · From the PDF
Image 4
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FIGURE 5 The effect of anticancer drugs on HSP60, HSP70, and HSP90 expression in HepG2 cell-derived exosomes. Exosomes, collected from HepG2 cell culture medium under basal conditions ( 1 ) or in the presence of paclitaxel ( 2 ), etoposide ( 3 ), irinotecan hydrochloride ( 4 ), or carboplatin ( 5 ), were separated on 12% SDS gel and examined by Western blotting using antibodies specific for HSP60, HSP70, and HSP90. Exposure of HepG2 cells to resistant anticancer drugs (irinotecan hydrochloride and carboplatin) considerably increased the content of HSP60, HSP70, and HSP90 compared with cells exposed to sensitive anticancer drugs (paclitaxel and etoposide) or under basal conditions ( p < 0.05). Control loading is shown by GADPH. Densities of the bands are indicated at the bottom . One representative experiment of three is shown.
FIGURE 5 The effect of anticancer drugs on HSP60, HSP70, and HSP90 expression in HepG2 cell-derived exosomes. Exosomes, collected from HepG2 cell culture medium under basal conditions ( 1 ) or in the presence of paclitaxel ( 2 ), etoposide ( 3 ), irinotecan hydrochloride ( 4 ), or carboplatin ( 5 ), were separated on 12% SDS gel and examined by Western blotting using antibodies specific for HSP60, HSP70, and HSP90. Exposure of HepG2 cells to resistant anticancer drugs (irinotecan hydrochloride and carboplatin) considerably increased the content of HSP60, HSP70, and HSP90 compared with cells exposed to sensitive anticancer drugs (paclitaxel and etoposide) or under basal conditions ( p < 0.05). Control loading is shown by GADPH. Densities of the bands are indicated at the bottom . One representative experiment of three is shown.CC-BY · From the PDF
FIGURE 6 Assessment of HSP60, HSP70, and HSP90 expression on the surface of exosomes secreted by HepG2 cells under both basal and stressinduced conditions. Exosomes, derived from HepG2 cells subjected to heat shock, anticancer drugs, or under basal conditions, were subsequently immobilized onto latex beads, and surface HSP expression was analyzed by flow cytometry. Elevated levels of HSP60, HSP70, and HSP90 were observed under stress-induced conditions as compared with basal conditions ( p < 0.05). The values for the mean fluorescence intensity ( MFI ) are presented as the mean ± S.D. of three independent experiments with similar results.
FIGURE 6 Assessment of HSP60, HSP70, and HSP90 expression on the surface of exosomes secreted by HepG2 cells under both basal and stressinduced conditions. Exosomes, derived from HepG2 cells subjected to heat shock, anticancer drugs, or under basal conditions, were subsequently immobilized onto latex beads, and surface HSP expression was analyzed by flow cytometry. Elevated levels of HSP60, HSP70, and HSP90 were observed under stress-induced conditions as compared with basal conditions ( p < 0.05). The values for the mean fluorescence intensity ( MFI ) are presented as the mean ± S.D. of three independent experiments with similar results.CC-BY · From the PDF
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Metadata

Authors
Lv, L.-H., Wan, Y.-L., Lin, Y., Zhang, W., Yang, M., Li, G.-L., Lin, H.-M., Shang, C.-Z., Chen, Y.-J., & Min, J.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2012-05
Volume
287
Issue
19
Pages
15874-15885
ISSN
0021-9258
DOI
10.1074/jbc.m112.340588
Cited by
420
References
2
Language
en
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