Host response to short-term, single-agent chemotherapy induces matrix metalloproteinase-9 expression and accelerates metastasis in mice

Svetlana Gingis-Velitski, David Loven, Liat Benayoun, Michal Munster, Rotem Bril, Tali Voloshin, Dror Alishekevitz, Francesco Bertolini, Yuval Shaked

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Mounting evidence suggests that bone marrow-derived cells (BMDC) contribute to tumor growth, angiogenesis, and metastasis. In acute reactions to cancer therapy, several types of BMDCs are rapidly mobilized to home tumors. Although this host reaction to therapy can promote tumor regrowth, its contribution to metastasis has not been explored. To focus only on the effects of chemotherapy on the host, we studied non-tumor-bearing mice. Plasma from animals treated with the chemotherapy paclitaxel induced angiogenesis, migration, and invasion of tumor cells along with host cell colonization. Lesser effects were seen with the chemotherapy gemcitabine. Conditioned medium from BMDCs and plasma from chemotherapy-treated mice each promoted metastatic properties in tumor cells by inducing matrix metalloproteinase-9 (MMP9) and epithelial-to-mesenchymal transition. In mice in which Lewis lung carcinoma cells were injected intravenously, treatment with paclitaxel, but not gemcitabine or vehicle, accelerated metastases in a manner that could be blocked by an MMP9 inhibitor. Moreover, chimeric mice reconstituted with BMDC where MMP9 activity was attenuated did not support accelerated metastasis by carcinoma cells that were pretreated with chemotherapy before their introduction to host animals. Taken together, our findings illustrate how some chemotherapies can exert prometastatic effects that may confound treatment outcomes.

Original languageEnglish
Pages (from-to)6986-6996
Number of pages11
JournalCancer Research
Volume71
Issue number22
DOIs
Publication statusPublished - Nov 15 2011

Fingerprint

Matrix Metalloproteinase 9
gemcitabine
Neoplasm Metastasis
Drug Therapy
Neoplasms
Paclitaxel
Bone Marrow Cells
Lewis Lung Carcinoma
Epithelial-Mesenchymal Transition
Matrix Metalloproteinase Inhibitors
Conditioned Culture Medium
Therapeutics
Carcinoma
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Host response to short-term, single-agent chemotherapy induces matrix metalloproteinase-9 expression and accelerates metastasis in mice. / Gingis-Velitski, Svetlana; Loven, David; Benayoun, Liat; Munster, Michal; Bril, Rotem; Voloshin, Tali; Alishekevitz, Dror; Bertolini, Francesco; Shaked, Yuval.

In: Cancer Research, Vol. 71, No. 22, 15.11.2011, p. 6986-6996.

Research output: Contribution to journalArticle

Gingis-Velitski, S, Loven, D, Benayoun, L, Munster, M, Bril, R, Voloshin, T, Alishekevitz, D, Bertolini, F & Shaked, Y 2011, 'Host response to short-term, single-agent chemotherapy induces matrix metalloproteinase-9 expression and accelerates metastasis in mice', Cancer Research, vol. 71, no. 22, pp. 6986-6996. https://doi.org/10.1158/0008-5472.CAN-11-0629
Gingis-Velitski, Svetlana ; Loven, David ; Benayoun, Liat ; Munster, Michal ; Bril, Rotem ; Voloshin, Tali ; Alishekevitz, Dror ; Bertolini, Francesco ; Shaked, Yuval. / Host response to short-term, single-agent chemotherapy induces matrix metalloproteinase-9 expression and accelerates metastasis in mice. In: Cancer Research. 2011 ; Vol. 71, No. 22. pp. 6986-6996.
@article{bd9e5d57072346519b0fbc6eeee246a1,
title = "Host response to short-term, single-agent chemotherapy induces matrix metalloproteinase-9 expression and accelerates metastasis in mice",
abstract = "Mounting evidence suggests that bone marrow-derived cells (BMDC) contribute to tumor growth, angiogenesis, and metastasis. In acute reactions to cancer therapy, several types of BMDCs are rapidly mobilized to home tumors. Although this host reaction to therapy can promote tumor regrowth, its contribution to metastasis has not been explored. To focus only on the effects of chemotherapy on the host, we studied non-tumor-bearing mice. Plasma from animals treated with the chemotherapy paclitaxel induced angiogenesis, migration, and invasion of tumor cells along with host cell colonization. Lesser effects were seen with the chemotherapy gemcitabine. Conditioned medium from BMDCs and plasma from chemotherapy-treated mice each promoted metastatic properties in tumor cells by inducing matrix metalloproteinase-9 (MMP9) and epithelial-to-mesenchymal transition. In mice in which Lewis lung carcinoma cells were injected intravenously, treatment with paclitaxel, but not gemcitabine or vehicle, accelerated metastases in a manner that could be blocked by an MMP9 inhibitor. Moreover, chimeric mice reconstituted with BMDC where MMP9 activity was attenuated did not support accelerated metastasis by carcinoma cells that were pretreated with chemotherapy before their introduction to host animals. Taken together, our findings illustrate how some chemotherapies can exert prometastatic effects that may confound treatment outcomes.",
author = "Svetlana Gingis-Velitski and David Loven and Liat Benayoun and Michal Munster and Rotem Bril and Tali Voloshin and Dror Alishekevitz and Francesco Bertolini and Yuval Shaked",
year = "2011",
month = "11",
day = "15",
doi = "10.1158/0008-5472.CAN-11-0629",
language = "English",
volume = "71",
pages = "6986--6996",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "22",

}

TY - JOUR

T1 - Host response to short-term, single-agent chemotherapy induces matrix metalloproteinase-9 expression and accelerates metastasis in mice

AU - Gingis-Velitski, Svetlana

AU - Loven, David

AU - Benayoun, Liat

AU - Munster, Michal

AU - Bril, Rotem

AU - Voloshin, Tali

AU - Alishekevitz, Dror

AU - Bertolini, Francesco

AU - Shaked, Yuval

PY - 2011/11/15

Y1 - 2011/11/15

N2 - Mounting evidence suggests that bone marrow-derived cells (BMDC) contribute to tumor growth, angiogenesis, and metastasis. In acute reactions to cancer therapy, several types of BMDCs are rapidly mobilized to home tumors. Although this host reaction to therapy can promote tumor regrowth, its contribution to metastasis has not been explored. To focus only on the effects of chemotherapy on the host, we studied non-tumor-bearing mice. Plasma from animals treated with the chemotherapy paclitaxel induced angiogenesis, migration, and invasion of tumor cells along with host cell colonization. Lesser effects were seen with the chemotherapy gemcitabine. Conditioned medium from BMDCs and plasma from chemotherapy-treated mice each promoted metastatic properties in tumor cells by inducing matrix metalloproteinase-9 (MMP9) and epithelial-to-mesenchymal transition. In mice in which Lewis lung carcinoma cells were injected intravenously, treatment with paclitaxel, but not gemcitabine or vehicle, accelerated metastases in a manner that could be blocked by an MMP9 inhibitor. Moreover, chimeric mice reconstituted with BMDC where MMP9 activity was attenuated did not support accelerated metastasis by carcinoma cells that were pretreated with chemotherapy before their introduction to host animals. Taken together, our findings illustrate how some chemotherapies can exert prometastatic effects that may confound treatment outcomes.

AB - Mounting evidence suggests that bone marrow-derived cells (BMDC) contribute to tumor growth, angiogenesis, and metastasis. In acute reactions to cancer therapy, several types of BMDCs are rapidly mobilized to home tumors. Although this host reaction to therapy can promote tumor regrowth, its contribution to metastasis has not been explored. To focus only on the effects of chemotherapy on the host, we studied non-tumor-bearing mice. Plasma from animals treated with the chemotherapy paclitaxel induced angiogenesis, migration, and invasion of tumor cells along with host cell colonization. Lesser effects were seen with the chemotherapy gemcitabine. Conditioned medium from BMDCs and plasma from chemotherapy-treated mice each promoted metastatic properties in tumor cells by inducing matrix metalloproteinase-9 (MMP9) and epithelial-to-mesenchymal transition. In mice in which Lewis lung carcinoma cells were injected intravenously, treatment with paclitaxel, but not gemcitabine or vehicle, accelerated metastases in a manner that could be blocked by an MMP9 inhibitor. Moreover, chimeric mice reconstituted with BMDC where MMP9 activity was attenuated did not support accelerated metastasis by carcinoma cells that were pretreated with chemotherapy before their introduction to host animals. Taken together, our findings illustrate how some chemotherapies can exert prometastatic effects that may confound treatment outcomes.

UR - http://www.scopus.com/inward/record.url?scp=81155132194&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=81155132194&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-11-0629

DO - 10.1158/0008-5472.CAN-11-0629

M3 - Article

VL - 71

SP - 6986

EP - 6996

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 22

ER -