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Published in: BMC Cancer 1/2005

Open Access 01-12-2005 | Research article

Acquisition of anoikis resistance in human osteosarcoma cells does not alter sensitivity to chemotherapeutic agents

Authors: C Marcela Díaz-Montero, Bradley W McIntyre

Published in: BMC Cancer | Issue 1/2005

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Abstract

Background

Chemotherapy-induced cell death can involve the induction of apoptosis. Thus, aberrant function of the pathways involved might result in chemoresistance. Since cell adhesion to the extracellular matrix acts as a survival factor that homeostatically maintains normal tissue architecture, it was tested whether acquisition of resistance to deadhesion-induced apoptosis (anoikis) in human osteosarcoma would result in resistance to chemotherapy.

Methods

Osteosarcoma cell lines (SAOS-2 and TE-85) obtained from ATCC and were maintained in complete Eagle's MEM medium. Suspension culture was established by placing cells in tissue culture wells coated with poly-HEMA. Cell cytotoxicity was determined using a live/dead cytotoxicity assay. Cell cycle/apoptosis analyses were performed using propidium iodide (PI) staining with subsequent FACS analysis. Apoptosis was also assayed by Annexin-FITC/PI staining.

Results

Etoposide, adriamycin, vinblastine, cisplatin and paclitaxel were able to induce apoptosis in human osteosarcoma cells SAOS-2 regardless of their anoikis resistance phenotype or the culture conditions (adhered vs. suspended). Moreover, suspended anoikis resistant TE-85 cells (TE-85ar) retained their sensitivity to chemotherapy as well.

Conclusion

Acquisition of anoikis resistance in human osteosarcoma cells does not result in a generalized resistance to all apoptotic stimuli, including chemotherapy. Moreover, our results suggest that the pathways regulating anoikis resistance and chemotherapy resistance might involve the action of different mediators.
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Literature
1.
go back to reference Hanahan D, Weinberg RA: The hallmarks of cancer. Cell. 2000, 100: 57-70. 10.1016/S0092-8674(00)81683-9.CrossRefPubMed Hanahan D, Weinberg RA: The hallmarks of cancer. Cell. 2000, 100: 57-70. 10.1016/S0092-8674(00)81683-9.CrossRefPubMed
2.
go back to reference Hickman JA: Apoptosis and tumourigenesis. Curr Opin Genet Dev. 2002, 12: 67-72. 10.1016/S0959-437X(01)00266-0.CrossRefPubMed Hickman JA: Apoptosis and tumourigenesis. Curr Opin Genet Dev. 2002, 12: 67-72. 10.1016/S0959-437X(01)00266-0.CrossRefPubMed
3.
go back to reference Frisch SM, Francis H: Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol. 1994, 124: 619-626. 10.1083/jcb.124.4.619.CrossRefPubMed Frisch SM, Francis H: Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol. 1994, 124: 619-626. 10.1083/jcb.124.4.619.CrossRefPubMed
5.
go back to reference Miranti CK, Brugge JS: Sensing the environment: a historical perspective on integrin signal transduction. Nat Cell Biol. 2002, 4: E83-90. 10.1038/ncb0402-e83.CrossRefPubMed Miranti CK, Brugge JS: Sensing the environment: a historical perspective on integrin signal transduction. Nat Cell Biol. 2002, 4: E83-90. 10.1038/ncb0402-e83.CrossRefPubMed
6.
go back to reference Giancotti FG, Ruoslahti E: Integrin signaling. Science. 1999, 285: 1028-1032. 10.1126/science.285.5430.1028.CrossRefPubMed Giancotti FG, Ruoslahti E: Integrin signaling. Science. 1999, 285: 1028-1032. 10.1126/science.285.5430.1028.CrossRefPubMed
7.
go back to reference Liu S, Calderwood DA, Ginsberg MH: Integrin cytoplasmic domain-binding proteins. J Cell Sci. 2000, 113 ( Pt 20): 3563-3571. Liu S, Calderwood DA, Ginsberg MH: Integrin cytoplasmic domain-binding proteins. J Cell Sci. 2000, 113 ( Pt 20): 3563-3571.
8.
go back to reference Cary LA, Guan JL: Focal adhesion kinase in integrin-mediated signaling. Front Biosci. 1999, 4: D102-13.CrossRefPubMed Cary LA, Guan JL: Focal adhesion kinase in integrin-mediated signaling. Front Biosci. 1999, 4: D102-13.CrossRefPubMed
9.
go back to reference Jones RJ, Brunton VG, Frame MC: Adhesion-linked kinases in cancer; emphasis on src, focal adhesion kinase and PI 3-kinase. Eur J Cancer. 2000, 36: 1595-1606. 10.1016/S0959-8049(00)00153-2.CrossRefPubMed Jones RJ, Brunton VG, Frame MC: Adhesion-linked kinases in cancer; emphasis on src, focal adhesion kinase and PI 3-kinase. Eur J Cancer. 2000, 36: 1595-1606. 10.1016/S0959-8049(00)00153-2.CrossRefPubMed
10.
go back to reference Turner CE: Paxillin and focal adhesion signalling. Nat Cell Biol. 2000, 2: E231-6. 10.1038/35046659.CrossRefPubMed Turner CE: Paxillin and focal adhesion signalling. Nat Cell Biol. 2000, 2: E231-6. 10.1038/35046659.CrossRefPubMed
11.
go back to reference Ravichandran KS: Signaling via Shc family adapter proteins. Oncogene. 2001, 20: 6322-6330. 10.1038/sj.onc.1204776.CrossRefPubMed Ravichandran KS: Signaling via Shc family adapter proteins. Oncogene. 2001, 20: 6322-6330. 10.1038/sj.onc.1204776.CrossRefPubMed
12.
go back to reference Miranti CK, Leng L, Maschberger P, Brugge JS, Shattil SJ: Identification of a novel integrin signaling pathway involving the kinase Syk and the guanine nucleotide exchange factor Vav1. Curr Biol. 1998, 8: 1289-1299. 10.1016/S0960-9822(07)00559-3.CrossRefPubMed Miranti CK, Leng L, Maschberger P, Brugge JS, Shattil SJ: Identification of a novel integrin signaling pathway involving the kinase Syk and the guanine nucleotide exchange factor Vav1. Curr Biol. 1998, 8: 1289-1299. 10.1016/S0960-9822(07)00559-3.CrossRefPubMed
13.
14.
go back to reference Shanmugathasan M, Jothy S: Apoptosis, anoikis and their relevance to the pathobiology of colon cancer. Pathol Int. 2000, 50: 273-279. 10.1046/j.1440-1827.2000.01047.x.CrossRefPubMed Shanmugathasan M, Jothy S: Apoptosis, anoikis and their relevance to the pathobiology of colon cancer. Pathol Int. 2000, 50: 273-279. 10.1046/j.1440-1827.2000.01047.x.CrossRefPubMed
15.
go back to reference Normanno N, De Luca A, Bianco C, Maiello MR, Carriero MV, Rehman A, Wechselberger C, Arra C, Strizzi L, Sanicola M, Salomon DS: Cripto-1 overexpression leads to enhanced invasiveness and resistance to anoikis in human MCF-7 breast cancer cells. J Cell Physiol. 2004, 198: 31-39. 10.1002/jcp.10375.CrossRefPubMed Normanno N, De Luca A, Bianco C, Maiello MR, Carriero MV, Rehman A, Wechselberger C, Arra C, Strizzi L, Sanicola M, Salomon DS: Cripto-1 overexpression leads to enhanced invasiveness and resistance to anoikis in human MCF-7 breast cancer cells. J Cell Physiol. 2004, 198: 31-39. 10.1002/jcp.10375.CrossRefPubMed
16.
go back to reference Swan EA, Jasser SA, Holsinger FC, Doan D, Bucana C, Myers JN: Acquisition of anoikis resistance is a critical step in the progression of oral tongue cancer. Oral Oncol. 2003, 39: 648-655. 10.1016/S1368-8375(03)00049-6.CrossRefPubMed Swan EA, Jasser SA, Holsinger FC, Doan D, Bucana C, Myers JN: Acquisition of anoikis resistance is a critical step in the progression of oral tongue cancer. Oral Oncol. 2003, 39: 648-655. 10.1016/S1368-8375(03)00049-6.CrossRefPubMed
17.
go back to reference Marco RAW, Diaz-Montero CM, N. WJ, Kleinerman ES, W. MIB: a4 Integrin increases anoikis of human osteosarcoma cells. J Cell Biochem. 2003, 88: 1038-1047. 10.1002/jcb.10465.CrossRefPubMed Marco RAW, Diaz-Montero CM, N. WJ, Kleinerman ES, W. MIB: a4 Integrin increases anoikis of human osteosarcoma cells. J Cell Biochem. 2003, 88: 1038-1047. 10.1002/jcb.10465.CrossRefPubMed
18.
go back to reference Diaz-Montero CM, McIntyre BW: Acquisition of anoikis resistance in human osteosarcoma cells. Eur J Cancer. 2003, 39: 2395-2402. 10.1016/S0959-8049(03)00575-6.CrossRefPubMed Diaz-Montero CM, McIntyre BW: Acquisition of anoikis resistance in human osteosarcoma cells. Eur J Cancer. 2003, 39: 2395-2402. 10.1016/S0959-8049(03)00575-6.CrossRefPubMed
19.
go back to reference Ferguson WS, Goorin AM: Current treatment of osteosarcoma. Cancer Invest. 2001, 19: 292-315. 10.1081/CNV-100102557.CrossRefPubMed Ferguson WS, Goorin AM: Current treatment of osteosarcoma. Cancer Invest. 2001, 19: 292-315. 10.1081/CNV-100102557.CrossRefPubMed
20.
go back to reference Bacci G, Briccoli A, Rocca M, Ferrari S, Donati D, Longhi A, Bertoni F, Bacchini P, Giacomini S, Forni C, Manfrini M, Galletti S: Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation: recent experience at the Rizzoli Institute in 57 patients treated with cisplatin, doxorubicin, and a high dose of methotrexate and ifosfamide. Ann Oncol. 2003, 14: 1126-1134. 10.1093/annonc/mdg286.CrossRefPubMed Bacci G, Briccoli A, Rocca M, Ferrari S, Donati D, Longhi A, Bertoni F, Bacchini P, Giacomini S, Forni C, Manfrini M, Galletti S: Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation: recent experience at the Rizzoli Institute in 57 patients treated with cisplatin, doxorubicin, and a high dose of methotrexate and ifosfamide. Ann Oncol. 2003, 14: 1126-1134. 10.1093/annonc/mdg286.CrossRefPubMed
21.
go back to reference Borges-Walmsley MI, McKeegan KS, Walmsley AR: Structure and function of efflux pumps that confer resistance to drugs. Biochem J. 2003, 376: 313-338. 10.1042/BJ20020957.CrossRefPubMedPubMedCentral Borges-Walmsley MI, McKeegan KS, Walmsley AR: Structure and function of efflux pumps that confer resistance to drugs. Biochem J. 2003, 376: 313-338. 10.1042/BJ20020957.CrossRefPubMedPubMedCentral
22.
go back to reference Schmitt CA, Lowe SW: Apoptosis and therapy. J Pathol. 1999, 187: 127-137. 10.1002/(SICI)1096-9896(199901)187:1<127::AID-PATH251>3.3.CO;2-K.CrossRefPubMed Schmitt CA, Lowe SW: Apoptosis and therapy. J Pathol. 1999, 187: 127-137. 10.1002/(SICI)1096-9896(199901)187:1<127::AID-PATH251>3.3.CO;2-K.CrossRefPubMed
23.
24.
go back to reference Kim R, Toge T: Changes in therapy for solid tumors: potential for overcoming drug resistance in vivo with molecular targeting agents. Surg Today. 2004, 34: 293-303. 10.1007/s00595-003-2710-4.CrossRefPubMed Kim R, Toge T: Changes in therapy for solid tumors: potential for overcoming drug resistance in vivo with molecular targeting agents. Surg Today. 2004, 34: 293-303. 10.1007/s00595-003-2710-4.CrossRefPubMed
25.
go back to reference Schmitt CA, Fridman JS, Yang M, Lee S, Baranov E, Hoffman RM, Lowe SW: A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell. 2002, 109: 335-346. 10.1016/S0092-8674(02)00734-1.CrossRefPubMed Schmitt CA, Fridman JS, Yang M, Lee S, Baranov E, Hoffman RM, Lowe SW: A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell. 2002, 109: 335-346. 10.1016/S0092-8674(02)00734-1.CrossRefPubMed
26.
go back to reference Chang BD, Swift ME, Shen M, Fang J, Broude EV, Roninson IB: Molecular determinants of terminal growth arrest induced in tumor cells by a chemotherapeutic agent. Proc Natl Acad Sci U S A. 2002, 99: 389-394. 10.1073/pnas.012602599.CrossRefPubMed Chang BD, Swift ME, Shen M, Fang J, Broude EV, Roninson IB: Molecular determinants of terminal growth arrest induced in tumor cells by a chemotherapeutic agent. Proc Natl Acad Sci U S A. 2002, 99: 389-394. 10.1073/pnas.012602599.CrossRefPubMed
27.
go back to reference Matsunaga T, Takemoto N, Sato T, Takimoto R, Tanaka I, Fujimi A, Akiyama T, Kuroda H, Kawano Y, Kobune M, Kato J, Hirayama Y, Sakamaki S, Kohda K, Miyake K, Niitsu Y: Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia. Nat Med. 2003, 9: 1158-1165. 10.1038/nm909.CrossRefPubMed Matsunaga T, Takemoto N, Sato T, Takimoto R, Tanaka I, Fujimi A, Akiyama T, Kuroda H, Kawano Y, Kobune M, Kato J, Hirayama Y, Sakamaki S, Kohda K, Miyake K, Niitsu Y: Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia. Nat Med. 2003, 9: 1158-1165. 10.1038/nm909.CrossRefPubMed
28.
go back to reference Frisch SM, Ruoslahti E: Integrins and anoikis. Curr Opin Cell Biol. 1997, 9: 701-706. 10.1016/S0955-0674(97)80124-X.CrossRefPubMed Frisch SM, Ruoslahti E: Integrins and anoikis. Curr Opin Cell Biol. 1997, 9: 701-706. 10.1016/S0955-0674(97)80124-X.CrossRefPubMed
29.
go back to reference Frisch SM, Screaton RA: Anoikis mechanisms. Curr Opin Cell Biol. 2001, 13: 555-562. 10.1016/S0955-0674(00)00251-9.CrossRefPubMed Frisch SM, Screaton RA: Anoikis mechanisms. Curr Opin Cell Biol. 2001, 13: 555-562. 10.1016/S0955-0674(00)00251-9.CrossRefPubMed
30.
go back to reference Grossmann J: Molecular mechanisms of "detachment-induced apoptosis-Anoikis". Apoptosis. 2002, 7: 247-260. 10.1023/A:1015312119693.CrossRefPubMed Grossmann J: Molecular mechanisms of "detachment-induced apoptosis-Anoikis". Apoptosis. 2002, 7: 247-260. 10.1023/A:1015312119693.CrossRefPubMed
31.
go back to reference Douma S, Van Laar T, Zevenhoven J, Meuwissen R, Van Garderen E, Peeper DS: Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. Nature. 2004, 430: 1034-1039. 10.1038/nature02765.CrossRefPubMed Douma S, Van Laar T, Zevenhoven J, Meuwissen R, Van Garderen E, Peeper DS: Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. Nature. 2004, 430: 1034-1039. 10.1038/nature02765.CrossRefPubMed
32.
go back to reference Nicholson KM, Anderson NG: The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal. 2002, 14: 381-395. 10.1016/S0898-6568(01)00271-6.CrossRefPubMed Nicholson KM, Anderson NG: The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal. 2002, 14: 381-395. 10.1016/S0898-6568(01)00271-6.CrossRefPubMed
33.
go back to reference Yamada KM, Araki M: Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci. 2001, 114: 2375-2382.PubMed Yamada KM, Araki M: Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci. 2001, 114: 2375-2382.PubMed
34.
go back to reference Scheid MP, Woodgett JR: Unravelling the activation mechanisms of protein kinase B/Akt. FEBS Lett. 2003, 546: 108-112. 10.1016/S0014-5793(03)00562-3.CrossRefPubMed Scheid MP, Woodgett JR: Unravelling the activation mechanisms of protein kinase B/Akt. FEBS Lett. 2003, 546: 108-112. 10.1016/S0014-5793(03)00562-3.CrossRefPubMed
35.
go back to reference Schmidt M, Hovelmann S, Beckers TL: A novel form of constitutively active farnesylated Akt1 prevents mammary epithelial cells from anoikis and suppresses chemotherapy-induced apoptosis. Br J Cancer. 2002, 87: 924-932. 10.1038/sj.bjc.6600566.CrossRefPubMedPubMedCentral Schmidt M, Hovelmann S, Beckers TL: A novel form of constitutively active farnesylated Akt1 prevents mammary epithelial cells from anoikis and suppresses chemotherapy-induced apoptosis. Br J Cancer. 2002, 87: 924-932. 10.1038/sj.bjc.6600566.CrossRefPubMedPubMedCentral
36.
go back to reference Duxbury MS, Ito H, Benoit E, Waseem T, Ashley SW, Whang EE: A novel role for carcinoembryonic antigen-related cell adhesion molecule 6 as a determinant of gemcitabine chemoresistance in pancreatic adenocarcinoma cells. Cancer Res. 2004, 64: 3987-3993.CrossRefPubMed Duxbury MS, Ito H, Benoit E, Waseem T, Ashley SW, Whang EE: A novel role for carcinoembryonic antigen-related cell adhesion molecule 6 as a determinant of gemcitabine chemoresistance in pancreatic adenocarcinoma cells. Cancer Res. 2004, 64: 3987-3993.CrossRefPubMed
37.
go back to reference Wang SC, Makino K, Xia W, Kim JS, Im SA, Peng H, Mok SC, Singletary SE, Hung MC: DOC-2/hDab-2 inhibits ILK activity and induces anoikis in breast cancer cells through an Akt-independent pathway. Oncogene. 2001, 20: 6960-6964. 10.1038/sj.onc.1204873.CrossRefPubMed Wang SC, Makino K, Xia W, Kim JS, Im SA, Peng H, Mok SC, Singletary SE, Hung MC: DOC-2/hDab-2 inhibits ILK activity and induces anoikis in breast cancer cells through an Akt-independent pathway. Oncogene. 2001, 20: 6960-6964. 10.1038/sj.onc.1204873.CrossRefPubMed
Metadata
Title
Acquisition of anoikis resistance in human osteosarcoma cells does not alter sensitivity to chemotherapeutic agents
Authors
C Marcela Díaz-Montero
Bradley W McIntyre
Publication date
01-12-2005
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2005
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-5-39

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