Migration deficit in monocyte-macrophages in human ovarian cancer

Ralph S. Freedman, Qing Ma, Ena Wang, Stacie T. Gallardo, Ilyssa O. Gordon, Jeong Won Shin, Ping Jin, David Stroncek, Francesco M. Marincola

Research output: Contribution to journalArticle

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Abstract

Purpose: To examine the migration responses of monocyte/macrophages (MO/MA) expressing complementary receptors to chemokines produced in the tumor environment of epithelial ovarian cancer (EOC). Methods: We examined the expression of the chemokine receptors, CCR1, CCR5, and CXCR4, on EOC associated ascitic and blood MO/MA; their response to complementary chemokines in a MO/MA migration assay and the F-actin content in an actin polymerization assay. A validated cDNA microarray assay was then utilized to examine alterations in pathway genes that can be identified with cell migration. Results: Ascitic and EOC blood MO/MA express CCR1, CCR5 and CXCR4, but differently. Cell surface expression levels for CCR1 and CCR5 were higher in ascites than that of normal blood in contrast to CXCR4 levels in ascitic MO/MA which were lower. EOC associated ascitic or blood MO/MA failed to migrate in response to the CC ligand RANTES and to the CXCR4 reactive chemokine, SDF1 (CXCL12). Ascitic and most EOC blood MO/MA also behaved differently from normal blood MO in the polymerization/depolymerization assay. A cDNA gene analysis of purified ascitic MO/MA demonstrated that a number of genes involved with chemokine production, focal adhesion, actin cytoskeletal function and leukocyte transendothelial migration were down-regulated in the ascitic MO/MA when compared to normal blood MO. Moreover, PBMC cDNA from EOC patients' blood also showed gene profiles similar to that of ascitic MO/MA. Conclusions: Defective migration and polymerization/depolymerization activity of MO/MA from EOC patients and a significant down-regulation of critical pathway genes suggest that other mechanisms might be involved in the accumulation of systemically derived MO at the tumor site of EOC patients.

Original languageEnglish
Pages (from-to)635-645
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume57
Issue number5
DOIs
Publication statusPublished - May 2008
Externally publishedYes

Fingerprint

Ovarian Neoplasms
Monocytes
Macrophages
Polymerization
Actins
Chemokine Receptors
Genes
Chemokines
Complementary DNA
Transendothelial and Transepithelial Migration
Chemokine CXCL12
Chemokine CCL5
Focal Adhesions
Critical Pathways
Ovarian epithelial cancer
Oligonucleotide Array Sequence Analysis
Ascites
Cell Movement
Neoplasms
Leukocytes

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Oncology

Cite this

Freedman, R. S., Ma, Q., Wang, E., Gallardo, S. T., Gordon, I. O., Shin, J. W., ... Marincola, F. M. (2008). Migration deficit in monocyte-macrophages in human ovarian cancer. Cancer Immunology, Immunotherapy, 57(5), 635-645. https://doi.org/10.1007/s00262-007-0401-5

Migration deficit in monocyte-macrophages in human ovarian cancer. / Freedman, Ralph S.; Ma, Qing; Wang, Ena; Gallardo, Stacie T.; Gordon, Ilyssa O.; Shin, Jeong Won; Jin, Ping; Stroncek, David; Marincola, Francesco M.

In: Cancer Immunology, Immunotherapy, Vol. 57, No. 5, 05.2008, p. 635-645.

Research output: Contribution to journalArticle

Freedman, RS, Ma, Q, Wang, E, Gallardo, ST, Gordon, IO, Shin, JW, Jin, P, Stroncek, D & Marincola, FM 2008, 'Migration deficit in monocyte-macrophages in human ovarian cancer', Cancer Immunology, Immunotherapy, vol. 57, no. 5, pp. 635-645. https://doi.org/10.1007/s00262-007-0401-5
Freedman, Ralph S. ; Ma, Qing ; Wang, Ena ; Gallardo, Stacie T. ; Gordon, Ilyssa O. ; Shin, Jeong Won ; Jin, Ping ; Stroncek, David ; Marincola, Francesco M. / Migration deficit in monocyte-macrophages in human ovarian cancer. In: Cancer Immunology, Immunotherapy. 2008 ; Vol. 57, No. 5. pp. 635-645.
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abstract = "Purpose: To examine the migration responses of monocyte/macrophages (MO/MA) expressing complementary receptors to chemokines produced in the tumor environment of epithelial ovarian cancer (EOC). Methods: We examined the expression of the chemokine receptors, CCR1, CCR5, and CXCR4, on EOC associated ascitic and blood MO/MA; their response to complementary chemokines in a MO/MA migration assay and the F-actin content in an actin polymerization assay. A validated cDNA microarray assay was then utilized to examine alterations in pathway genes that can be identified with cell migration. Results: Ascitic and EOC blood MO/MA express CCR1, CCR5 and CXCR4, but differently. Cell surface expression levels for CCR1 and CCR5 were higher in ascites than that of normal blood in contrast to CXCR4 levels in ascitic MO/MA which were lower. EOC associated ascitic or blood MO/MA failed to migrate in response to the CC ligand RANTES and to the CXCR4 reactive chemokine, SDF1 (CXCL12). Ascitic and most EOC blood MO/MA also behaved differently from normal blood MO in the polymerization/depolymerization assay. A cDNA gene analysis of purified ascitic MO/MA demonstrated that a number of genes involved with chemokine production, focal adhesion, actin cytoskeletal function and leukocyte transendothelial migration were down-regulated in the ascitic MO/MA when compared to normal blood MO. Moreover, PBMC cDNA from EOC patients' blood also showed gene profiles similar to that of ascitic MO/MA. Conclusions: Defective migration and polymerization/depolymerization activity of MO/MA from EOC patients and a significant down-regulation of critical pathway genes suggest that other mechanisms might be involved in the accumulation of systemically derived MO at the tumor site of EOC patients.",
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AU - Freedman, Ralph S.

AU - Ma, Qing

AU - Wang, Ena

AU - Gallardo, Stacie T.

AU - Gordon, Ilyssa O.

AU - Shin, Jeong Won

AU - Jin, Ping

AU - Stroncek, David

AU - Marincola, Francesco M.

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N2 - Purpose: To examine the migration responses of monocyte/macrophages (MO/MA) expressing complementary receptors to chemokines produced in the tumor environment of epithelial ovarian cancer (EOC). Methods: We examined the expression of the chemokine receptors, CCR1, CCR5, and CXCR4, on EOC associated ascitic and blood MO/MA; their response to complementary chemokines in a MO/MA migration assay and the F-actin content in an actin polymerization assay. A validated cDNA microarray assay was then utilized to examine alterations in pathway genes that can be identified with cell migration. Results: Ascitic and EOC blood MO/MA express CCR1, CCR5 and CXCR4, but differently. Cell surface expression levels for CCR1 and CCR5 were higher in ascites than that of normal blood in contrast to CXCR4 levels in ascitic MO/MA which were lower. EOC associated ascitic or blood MO/MA failed to migrate in response to the CC ligand RANTES and to the CXCR4 reactive chemokine, SDF1 (CXCL12). Ascitic and most EOC blood MO/MA also behaved differently from normal blood MO in the polymerization/depolymerization assay. A cDNA gene analysis of purified ascitic MO/MA demonstrated that a number of genes involved with chemokine production, focal adhesion, actin cytoskeletal function and leukocyte transendothelial migration were down-regulated in the ascitic MO/MA when compared to normal blood MO. Moreover, PBMC cDNA from EOC patients' blood also showed gene profiles similar to that of ascitic MO/MA. Conclusions: Defective migration and polymerization/depolymerization activity of MO/MA from EOC patients and a significant down-regulation of critical pathway genes suggest that other mechanisms might be involved in the accumulation of systemically derived MO at the tumor site of EOC patients.

AB - Purpose: To examine the migration responses of monocyte/macrophages (MO/MA) expressing complementary receptors to chemokines produced in the tumor environment of epithelial ovarian cancer (EOC). Methods: We examined the expression of the chemokine receptors, CCR1, CCR5, and CXCR4, on EOC associated ascitic and blood MO/MA; their response to complementary chemokines in a MO/MA migration assay and the F-actin content in an actin polymerization assay. A validated cDNA microarray assay was then utilized to examine alterations in pathway genes that can be identified with cell migration. Results: Ascitic and EOC blood MO/MA express CCR1, CCR5 and CXCR4, but differently. Cell surface expression levels for CCR1 and CCR5 were higher in ascites than that of normal blood in contrast to CXCR4 levels in ascitic MO/MA which were lower. EOC associated ascitic or blood MO/MA failed to migrate in response to the CC ligand RANTES and to the CXCR4 reactive chemokine, SDF1 (CXCL12). Ascitic and most EOC blood MO/MA also behaved differently from normal blood MO in the polymerization/depolymerization assay. A cDNA gene analysis of purified ascitic MO/MA demonstrated that a number of genes involved with chemokine production, focal adhesion, actin cytoskeletal function and leukocyte transendothelial migration were down-regulated in the ascitic MO/MA when compared to normal blood MO. Moreover, PBMC cDNA from EOC patients' blood also showed gene profiles similar to that of ascitic MO/MA. Conclusions: Defective migration and polymerization/depolymerization activity of MO/MA from EOC patients and a significant down-regulation of critical pathway genes suggest that other mechanisms might be involved in the accumulation of systemically derived MO at the tumor site of EOC patients.

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