Paracrine regulation of colony-stimulating factor-1 in medulloblastoma

Implications for pathogenesis and therapeutic interventions

Achilles K. Papavasiliou, Mark F. Mehler, Peter C. Mabie, Ronen Marmur, Song Qingbin, Robert F. Keating, John A. Kessler

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

OBJECTIVE: Colony-stimulating factor (CSF)-1, a chemotactic and mitogenic factor for macrophages and microglia, is expressed in a variety of nervous system tumors and when present in nonneural malignancies, is associated with marked inflammatory infiltrates, dissemination, and poorer prognosis. This study investigated the paracrine effects of CSF-1 production by medulloblastoma cells on the macrophage/microglial lineage. METHODS: A recurrent metastatic desmoplastic medulloblastoma was isolated from a 26- year-old man and propagated in tissue culture. Cellular phenotype and proliferation were assessed by immunocytochemical techniques; transcript expression for CSF-1, granulocyte macrophage-CSF, interleukin-3, and c-fms (the receptor for CSF-1) was examined with reverse transcriptase-polymerase chain reaction; and conditioned media and coculture paradigms were used to study cytokine effects on cellular proliferation. RESULTS: Serially passaged cells were uniformly immunoreactive for two lineage-independent neuroepithelial markers, nestin and vimentin. A subpopulation of cells with morphological characteristics of early differentiation stained for neurofilament 66 (7%) and microtubule-associated protein (5%) (markers of early neuronal precursors and postmitotic neurons, respectively) and for the Yp subunit of glutathione-S-transferase (3%) (a marker of early oligodendroglial progenitors). Tumor cells expressed transcripts for CSF-1, but not for granulocyte macrophage-CSF, interleukin-3, or c-fms. Treatment of microglia with serum-free medulloblastoma-conditioned media significantly increased proliferation (P < 0.001), suggesting the secretion of CSF-1. Coculture of medulloblastoma cells and microglia significantly increased proliferation of both cell types (each condition, P < 0.01). CONCLUSION: These observations suggest that CSF-1 mediates important paracrine interactions between transformed cells and the immune system, resulting in increased growth rate and metastatic potential. Future therapeutic goals need to include immunotherapeutic protocols to modulate this interaction.

Original languageEnglish (US)
Pages (from-to)916-923
Number of pages8
JournalNeurosurgery
Volume41
Issue number4
DOIs
StatePublished - Oct 1997

Fingerprint

Medulloblastoma
Macrophage Colony-Stimulating Factor
Microglia
Interleukin-3
Cell Proliferation
Granulocyte-Macrophage Colony-Stimulating Factor
Conditioned Culture Medium
Coculture Techniques
Therapeutics
Nervous System Neoplasms
Nestin
Microtubule-Associated Proteins
Chemotactic Factors
Vimentin
Glutathione Transferase
Reverse Transcriptase Polymerase Chain Reaction
Immune System
Neoplasms
Macrophages
Cytokines

Keywords

  • Colony-stimulating factor-1
  • Macrophages
  • Medulloblastoma
  • Primitive neuroectodermal tumor

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Paracrine regulation of colony-stimulating factor-1 in medulloblastoma : Implications for pathogenesis and therapeutic interventions. / Papavasiliou, Achilles K.; Mehler, Mark F.; Mabie, Peter C.; Marmur, Ronen; Qingbin, Song; Keating, Robert F.; Kessler, John A.

In: Neurosurgery, Vol. 41, No. 4, 10.1997, p. 916-923.

Research output: Contribution to journalArticle

Papavasiliou, Achilles K. ; Mehler, Mark F. ; Mabie, Peter C. ; Marmur, Ronen ; Qingbin, Song ; Keating, Robert F. ; Kessler, John A. / Paracrine regulation of colony-stimulating factor-1 in medulloblastoma : Implications for pathogenesis and therapeutic interventions. In: Neurosurgery. 1997 ; Vol. 41, No. 4. pp. 916-923.
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abstract = "OBJECTIVE: Colony-stimulating factor (CSF)-1, a chemotactic and mitogenic factor for macrophages and microglia, is expressed in a variety of nervous system tumors and when present in nonneural malignancies, is associated with marked inflammatory infiltrates, dissemination, and poorer prognosis. This study investigated the paracrine effects of CSF-1 production by medulloblastoma cells on the macrophage/microglial lineage. METHODS: A recurrent metastatic desmoplastic medulloblastoma was isolated from a 26- year-old man and propagated in tissue culture. Cellular phenotype and proliferation were assessed by immunocytochemical techniques; transcript expression for CSF-1, granulocyte macrophage-CSF, interleukin-3, and c-fms (the receptor for CSF-1) was examined with reverse transcriptase-polymerase chain reaction; and conditioned media and coculture paradigms were used to study cytokine effects on cellular proliferation. RESULTS: Serially passaged cells were uniformly immunoreactive for two lineage-independent neuroepithelial markers, nestin and vimentin. A subpopulation of cells with morphological characteristics of early differentiation stained for neurofilament 66 (7{\%}) and microtubule-associated protein (5{\%}) (markers of early neuronal precursors and postmitotic neurons, respectively) and for the Yp subunit of glutathione-S-transferase (3{\%}) (a marker of early oligodendroglial progenitors). Tumor cells expressed transcripts for CSF-1, but not for granulocyte macrophage-CSF, interleukin-3, or c-fms. Treatment of microglia with serum-free medulloblastoma-conditioned media significantly increased proliferation (P < 0.001), suggesting the secretion of CSF-1. Coculture of medulloblastoma cells and microglia significantly increased proliferation of both cell types (each condition, P < 0.01). CONCLUSION: These observations suggest that CSF-1 mediates important paracrine interactions between transformed cells and the immune system, resulting in increased growth rate and metastatic potential. Future therapeutic goals need to include immunotherapeutic protocols to modulate this interaction.",
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T2 - Implications for pathogenesis and therapeutic interventions

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AU - Mehler, Mark F.

AU - Mabie, Peter C.

AU - Marmur, Ronen

AU - Qingbin, Song

AU - Keating, Robert F.

AU - Kessler, John A.

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N2 - OBJECTIVE: Colony-stimulating factor (CSF)-1, a chemotactic and mitogenic factor for macrophages and microglia, is expressed in a variety of nervous system tumors and when present in nonneural malignancies, is associated with marked inflammatory infiltrates, dissemination, and poorer prognosis. This study investigated the paracrine effects of CSF-1 production by medulloblastoma cells on the macrophage/microglial lineage. METHODS: A recurrent metastatic desmoplastic medulloblastoma was isolated from a 26- year-old man and propagated in tissue culture. Cellular phenotype and proliferation were assessed by immunocytochemical techniques; transcript expression for CSF-1, granulocyte macrophage-CSF, interleukin-3, and c-fms (the receptor for CSF-1) was examined with reverse transcriptase-polymerase chain reaction; and conditioned media and coculture paradigms were used to study cytokine effects on cellular proliferation. RESULTS: Serially passaged cells were uniformly immunoreactive for two lineage-independent neuroepithelial markers, nestin and vimentin. A subpopulation of cells with morphological characteristics of early differentiation stained for neurofilament 66 (7%) and microtubule-associated protein (5%) (markers of early neuronal precursors and postmitotic neurons, respectively) and for the Yp subunit of glutathione-S-transferase (3%) (a marker of early oligodendroglial progenitors). Tumor cells expressed transcripts for CSF-1, but not for granulocyte macrophage-CSF, interleukin-3, or c-fms. Treatment of microglia with serum-free medulloblastoma-conditioned media significantly increased proliferation (P < 0.001), suggesting the secretion of CSF-1. Coculture of medulloblastoma cells and microglia significantly increased proliferation of both cell types (each condition, P < 0.01). CONCLUSION: These observations suggest that CSF-1 mediates important paracrine interactions between transformed cells and the immune system, resulting in increased growth rate and metastatic potential. Future therapeutic goals need to include immunotherapeutic protocols to modulate this interaction.

AB - OBJECTIVE: Colony-stimulating factor (CSF)-1, a chemotactic and mitogenic factor for macrophages and microglia, is expressed in a variety of nervous system tumors and when present in nonneural malignancies, is associated with marked inflammatory infiltrates, dissemination, and poorer prognosis. This study investigated the paracrine effects of CSF-1 production by medulloblastoma cells on the macrophage/microglial lineage. METHODS: A recurrent metastatic desmoplastic medulloblastoma was isolated from a 26- year-old man and propagated in tissue culture. Cellular phenotype and proliferation were assessed by immunocytochemical techniques; transcript expression for CSF-1, granulocyte macrophage-CSF, interleukin-3, and c-fms (the receptor for CSF-1) was examined with reverse transcriptase-polymerase chain reaction; and conditioned media and coculture paradigms were used to study cytokine effects on cellular proliferation. RESULTS: Serially passaged cells were uniformly immunoreactive for two lineage-independent neuroepithelial markers, nestin and vimentin. A subpopulation of cells with morphological characteristics of early differentiation stained for neurofilament 66 (7%) and microtubule-associated protein (5%) (markers of early neuronal precursors and postmitotic neurons, respectively) and for the Yp subunit of glutathione-S-transferase (3%) (a marker of early oligodendroglial progenitors). Tumor cells expressed transcripts for CSF-1, but not for granulocyte macrophage-CSF, interleukin-3, or c-fms. Treatment of microglia with serum-free medulloblastoma-conditioned media significantly increased proliferation (P < 0.001), suggesting the secretion of CSF-1. Coculture of medulloblastoma cells and microglia significantly increased proliferation of both cell types (each condition, P < 0.01). CONCLUSION: These observations suggest that CSF-1 mediates important paracrine interactions between transformed cells and the immune system, resulting in increased growth rate and metastatic potential. Future therapeutic goals need to include immunotherapeutic protocols to modulate this interaction.

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