Improved response to nab-paclitaxel compared with cremophor-solubilized paclitaxel is independent of secreted protein acidic and rich in cysteine expression in non-small cell lung cancer

Huanjie Shao, Haikuo Tang, Oreste E. Salavaggione, Chunrong Yu, Bonnie Hylander, Wei Tan, Elizabeth Repasky, Alex Adjei, Grace K. Dy

Research output: Contribution to journalReview article

20 Citations (Scopus)

Abstract

Background: The secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein that is produced by tumor and/or neighboring stroma. SPARC expression is thought to facilitate the intracellular accumulation of nanoparticle albumin-bound paclitaxel (nab-paclitaxel, abraxane [ABX]). Gene hypermethylation is a common mechanism for loss of SPARC expression in non-small cell lung cancer (NSCLC). We aim to demonstrate the role of SPARC expression as biomarker for treatment selection using ABX in NSCLC and to evaluate the presence of synergistic antitumor effect when a demethylating agent is combined with ABX. Methods: We analyzed the SPARC messenger RNA expression and SPARC gene methylation status in 13 NSCLC cell lines and 22 minimally passaged patient-derived (PD) NSCLC tumors using real-time (RT) polymerase chain reaction. The effect of ABX on tumor growth was compared with cremophor-solubilized paclitaxel (taxol) in severe combined immunodeficiency mice bearing SPARC-positive PD xenografts. The effect of pretreatment with a demethylating agent, 5-Aza-2′-deoxycytidine (DEC) in SPARC-negative tumors was assessed. Results: SPARC expression was weak to absent in 62% of established NSCLC cell lines and 68% of PD NSCLC tumor xenografts. SPARC expression could be up-regulated/restored by DEC treatment in both SPARC-negative cell lines and PD xenografts in vitro and in vivo. ABX demonstrated better antitumor efficacy than equitoxic dose of taxol in SPARC-expressing xenografts and some SPARC-negative xenografts. At equimolar doses in vitro, there was similar increased cytotoxicity on DEC pretreatment with either ABX or taxol in SPARC-negative cell lines. At equitoxic doses, there was similar additive antitumor activity of DEC with either ABX or taxol in SPARC-negative PD xenografts. Conclusion: Endogenous SPARC status is somewhat uncorrelated with response to ABX in NSCLC. The greater antitumor effect of ABX compared with equitoxic dose of taxol observed in SPARC-expressing NSCLC tumors can also be seen in some SPARC-negative tumors. DEC pretreatment similarly enhanced antitumor activity with either ABX or taxol in SPARC-negative tumors.

Original languageEnglish (US)
Pages (from-to)998-1005
Number of pages8
JournalJournal of Thoracic Oncology
Volume6
Issue number6
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

Fingerprint

Paclitaxel
Non-Small Cell Lung Carcinoma
Cysteine
Proteins
Heterografts
Deoxycytidine
Neoplasms
130-nm albumin-bound paclitaxel
cremophor
Cell Line
decitabine
Albumin-Bound Paclitaxel
Severe Combined Immunodeficiency
Nanoparticles
Methylation

Keywords

  • 5-aza-2′- deoxycytidine
  • Cremophor-solubilized paclitaxel
  • Nab-paclitaxel
  • Non-small cell lung cancer (NSCLC)
  • SPARC

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Improved response to nab-paclitaxel compared with cremophor-solubilized paclitaxel is independent of secreted protein acidic and rich in cysteine expression in non-small cell lung cancer. / Shao, Huanjie; Tang, Haikuo; Salavaggione, Oreste E.; Yu, Chunrong; Hylander, Bonnie; Tan, Wei; Repasky, Elizabeth; Adjei, Alex; Dy, Grace K.

In: Journal of Thoracic Oncology, Vol. 6, No. 6, 01.01.2011, p. 998-1005.

Research output: Contribution to journalReview article

Shao, Huanjie ; Tang, Haikuo ; Salavaggione, Oreste E. ; Yu, Chunrong ; Hylander, Bonnie ; Tan, Wei ; Repasky, Elizabeth ; Adjei, Alex ; Dy, Grace K. / Improved response to nab-paclitaxel compared with cremophor-solubilized paclitaxel is independent of secreted protein acidic and rich in cysteine expression in non-small cell lung cancer. In: Journal of Thoracic Oncology. 2011 ; Vol. 6, No. 6. pp. 998-1005.
@article{386279b2fd6e4340aa1e431416b10f19,
title = "Improved response to nab-paclitaxel compared with cremophor-solubilized paclitaxel is independent of secreted protein acidic and rich in cysteine expression in non-small cell lung cancer",
abstract = "Background: The secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein that is produced by tumor and/or neighboring stroma. SPARC expression is thought to facilitate the intracellular accumulation of nanoparticle albumin-bound paclitaxel (nab-paclitaxel, abraxane [ABX]). Gene hypermethylation is a common mechanism for loss of SPARC expression in non-small cell lung cancer (NSCLC). We aim to demonstrate the role of SPARC expression as biomarker for treatment selection using ABX in NSCLC and to evaluate the presence of synergistic antitumor effect when a demethylating agent is combined with ABX. Methods: We analyzed the SPARC messenger RNA expression and SPARC gene methylation status in 13 NSCLC cell lines and 22 minimally passaged patient-derived (PD) NSCLC tumors using real-time (RT) polymerase chain reaction. The effect of ABX on tumor growth was compared with cremophor-solubilized paclitaxel (taxol) in severe combined immunodeficiency mice bearing SPARC-positive PD xenografts. The effect of pretreatment with a demethylating agent, 5-Aza-2′-deoxycytidine (DEC) in SPARC-negative tumors was assessed. Results: SPARC expression was weak to absent in 62{\%} of established NSCLC cell lines and 68{\%} of PD NSCLC tumor xenografts. SPARC expression could be up-regulated/restored by DEC treatment in both SPARC-negative cell lines and PD xenografts in vitro and in vivo. ABX demonstrated better antitumor efficacy than equitoxic dose of taxol in SPARC-expressing xenografts and some SPARC-negative xenografts. At equimolar doses in vitro, there was similar increased cytotoxicity on DEC pretreatment with either ABX or taxol in SPARC-negative cell lines. At equitoxic doses, there was similar additive antitumor activity of DEC with either ABX or taxol in SPARC-negative PD xenografts. Conclusion: Endogenous SPARC status is somewhat uncorrelated with response to ABX in NSCLC. The greater antitumor effect of ABX compared with equitoxic dose of taxol observed in SPARC-expressing NSCLC tumors can also be seen in some SPARC-negative tumors. DEC pretreatment similarly enhanced antitumor activity with either ABX or taxol in SPARC-negative tumors.",
keywords = "5-aza-2′- deoxycytidine, Cremophor-solubilized paclitaxel, Nab-paclitaxel, Non-small cell lung cancer (NSCLC), SPARC",
author = "Huanjie Shao and Haikuo Tang and Salavaggione, {Oreste E.} and Chunrong Yu and Bonnie Hylander and Wei Tan and Elizabeth Repasky and Alex Adjei and Dy, {Grace K.}",
year = "2011",
month = "1",
day = "1",
doi = "10.1097/JTO.0b013e318217b739",
language = "English (US)",
volume = "6",
pages = "998--1005",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
number = "6",

}

TY - JOUR

T1 - Improved response to nab-paclitaxel compared with cremophor-solubilized paclitaxel is independent of secreted protein acidic and rich in cysteine expression in non-small cell lung cancer

AU - Shao, Huanjie

AU - Tang, Haikuo

AU - Salavaggione, Oreste E.

AU - Yu, Chunrong

AU - Hylander, Bonnie

AU - Tan, Wei

AU - Repasky, Elizabeth

AU - Adjei, Alex

AU - Dy, Grace K.

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Background: The secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein that is produced by tumor and/or neighboring stroma. SPARC expression is thought to facilitate the intracellular accumulation of nanoparticle albumin-bound paclitaxel (nab-paclitaxel, abraxane [ABX]). Gene hypermethylation is a common mechanism for loss of SPARC expression in non-small cell lung cancer (NSCLC). We aim to demonstrate the role of SPARC expression as biomarker for treatment selection using ABX in NSCLC and to evaluate the presence of synergistic antitumor effect when a demethylating agent is combined with ABX. Methods: We analyzed the SPARC messenger RNA expression and SPARC gene methylation status in 13 NSCLC cell lines and 22 minimally passaged patient-derived (PD) NSCLC tumors using real-time (RT) polymerase chain reaction. The effect of ABX on tumor growth was compared with cremophor-solubilized paclitaxel (taxol) in severe combined immunodeficiency mice bearing SPARC-positive PD xenografts. The effect of pretreatment with a demethylating agent, 5-Aza-2′-deoxycytidine (DEC) in SPARC-negative tumors was assessed. Results: SPARC expression was weak to absent in 62% of established NSCLC cell lines and 68% of PD NSCLC tumor xenografts. SPARC expression could be up-regulated/restored by DEC treatment in both SPARC-negative cell lines and PD xenografts in vitro and in vivo. ABX demonstrated better antitumor efficacy than equitoxic dose of taxol in SPARC-expressing xenografts and some SPARC-negative xenografts. At equimolar doses in vitro, there was similar increased cytotoxicity on DEC pretreatment with either ABX or taxol in SPARC-negative cell lines. At equitoxic doses, there was similar additive antitumor activity of DEC with either ABX or taxol in SPARC-negative PD xenografts. Conclusion: Endogenous SPARC status is somewhat uncorrelated with response to ABX in NSCLC. The greater antitumor effect of ABX compared with equitoxic dose of taxol observed in SPARC-expressing NSCLC tumors can also be seen in some SPARC-negative tumors. DEC pretreatment similarly enhanced antitumor activity with either ABX or taxol in SPARC-negative tumors.

AB - Background: The secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein that is produced by tumor and/or neighboring stroma. SPARC expression is thought to facilitate the intracellular accumulation of nanoparticle albumin-bound paclitaxel (nab-paclitaxel, abraxane [ABX]). Gene hypermethylation is a common mechanism for loss of SPARC expression in non-small cell lung cancer (NSCLC). We aim to demonstrate the role of SPARC expression as biomarker for treatment selection using ABX in NSCLC and to evaluate the presence of synergistic antitumor effect when a demethylating agent is combined with ABX. Methods: We analyzed the SPARC messenger RNA expression and SPARC gene methylation status in 13 NSCLC cell lines and 22 minimally passaged patient-derived (PD) NSCLC tumors using real-time (RT) polymerase chain reaction. The effect of ABX on tumor growth was compared with cremophor-solubilized paclitaxel (taxol) in severe combined immunodeficiency mice bearing SPARC-positive PD xenografts. The effect of pretreatment with a demethylating agent, 5-Aza-2′-deoxycytidine (DEC) in SPARC-negative tumors was assessed. Results: SPARC expression was weak to absent in 62% of established NSCLC cell lines and 68% of PD NSCLC tumor xenografts. SPARC expression could be up-regulated/restored by DEC treatment in both SPARC-negative cell lines and PD xenografts in vitro and in vivo. ABX demonstrated better antitumor efficacy than equitoxic dose of taxol in SPARC-expressing xenografts and some SPARC-negative xenografts. At equimolar doses in vitro, there was similar increased cytotoxicity on DEC pretreatment with either ABX or taxol in SPARC-negative cell lines. At equitoxic doses, there was similar additive antitumor activity of DEC with either ABX or taxol in SPARC-negative PD xenografts. Conclusion: Endogenous SPARC status is somewhat uncorrelated with response to ABX in NSCLC. The greater antitumor effect of ABX compared with equitoxic dose of taxol observed in SPARC-expressing NSCLC tumors can also be seen in some SPARC-negative tumors. DEC pretreatment similarly enhanced antitumor activity with either ABX or taxol in SPARC-negative tumors.

KW - 5-aza-2′- deoxycytidine

KW - Cremophor-solubilized paclitaxel

KW - Nab-paclitaxel

KW - Non-small cell lung cancer (NSCLC)

KW - SPARC

UR - http://www.scopus.com/inward/record.url?scp=79958125714&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79958125714&partnerID=8YFLogxK

U2 - 10.1097/JTO.0b013e318217b739

DO - 10.1097/JTO.0b013e318217b739

M3 - Review article

VL - 6

SP - 998

EP - 1005

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

SN - 1556-0864

IS - 6

ER -