[Ca2+]i as a potential downregulator of α2β1-integrin-mediated A2058 tumor cell migration to type IV collagen

Louis Hodgson, Cheng Dong

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17 Citations (Scopus)

Abstract

We have investigated cellular Ca2+ regulation during A2058 human melanoma cell chemotaxis to type IV collagen (CIV). We have identified α2β1-integrin as the primary mediator of A2058 cell response to CIV in vitro. Integrin ligation initiated a characteristic intracellular Ca2+ concentration ([Ca2+]i) response consisting of an internal release and a receptor-mediated Ca2+ entry. Thapsigargin (TG) pretreatment drained overlapping and CIV-inducible internal Ca2+ stores while initiating a store-operated Ca2+ release (SOCR). CIV-mediated Ca2+ entry was additive to TG-SOCR, suggesting an independent signaling mechanism. Similarly, ionophore application in a basal medium containing Ca2+ initiated a sustained influx. Elevated [Ca2+]i from TG-SOCR or ionophore significantly attenuated cell migration to CIV by recruiting the Ca2+/calcineurin-mediated signaling pathway. Furthermore, low [Ca2+]i induced by EGTA application in the presence of ionophore fully restored cell motility to CIV. Together, these results suggest that [Ca2+]i signaling accompanying A2058 cell response to α2β1-integrin ligation is neither necessary nor sufficient and that elevated [Ca2+]i downregulates cell motility via a calcineurin-mediated mechanism in A2058 cell chemotaxis to CIV.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume281
Issue number1 50-1
StatePublished - 2001

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Collagen Type IV
Integrins
Cell Movement
Thapsigargin
Ionophores
Calcineurin
Chemotaxis
Ligation
Neoplasms
Egtazic Acid
Melanoma
Down-Regulation

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

Cite this

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title = "[Ca2+]i as a potential downregulator of α2β1-integrin-mediated A2058 tumor cell migration to type IV collagen",
abstract = "We have investigated cellular Ca2+ regulation during A2058 human melanoma cell chemotaxis to type IV collagen (CIV). We have identified α2β1-integrin as the primary mediator of A2058 cell response to CIV in vitro. Integrin ligation initiated a characteristic intracellular Ca2+ concentration ([Ca2+]i) response consisting of an internal release and a receptor-mediated Ca2+ entry. Thapsigargin (TG) pretreatment drained overlapping and CIV-inducible internal Ca2+ stores while initiating a store-operated Ca2+ release (SOCR). CIV-mediated Ca2+ entry was additive to TG-SOCR, suggesting an independent signaling mechanism. Similarly, ionophore application in a basal medium containing Ca2+ initiated a sustained influx. Elevated [Ca2+]i from TG-SOCR or ionophore significantly attenuated cell migration to CIV by recruiting the Ca2+/calcineurin-mediated signaling pathway. Furthermore, low [Ca2+]i induced by EGTA application in the presence of ionophore fully restored cell motility to CIV. Together, these results suggest that [Ca2+]i signaling accompanying A2058 cell response to α2β1-integrin ligation is neither necessary nor sufficient and that elevated [Ca2+]i downregulates cell motility via a calcineurin-mediated mechanism in A2058 cell chemotaxis to CIV.",
author = "Louis Hodgson and Cheng Dong",
year = "2001",
language = "English (US)",
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journal = "American Journal of Physiology",
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T1 - [Ca2+]i as a potential downregulator of α2β1-integrin-mediated A2058 tumor cell migration to type IV collagen

AU - Hodgson, Louis

AU - Dong, Cheng

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N2 - We have investigated cellular Ca2+ regulation during A2058 human melanoma cell chemotaxis to type IV collagen (CIV). We have identified α2β1-integrin as the primary mediator of A2058 cell response to CIV in vitro. Integrin ligation initiated a characteristic intracellular Ca2+ concentration ([Ca2+]i) response consisting of an internal release and a receptor-mediated Ca2+ entry. Thapsigargin (TG) pretreatment drained overlapping and CIV-inducible internal Ca2+ stores while initiating a store-operated Ca2+ release (SOCR). CIV-mediated Ca2+ entry was additive to TG-SOCR, suggesting an independent signaling mechanism. Similarly, ionophore application in a basal medium containing Ca2+ initiated a sustained influx. Elevated [Ca2+]i from TG-SOCR or ionophore significantly attenuated cell migration to CIV by recruiting the Ca2+/calcineurin-mediated signaling pathway. Furthermore, low [Ca2+]i induced by EGTA application in the presence of ionophore fully restored cell motility to CIV. Together, these results suggest that [Ca2+]i signaling accompanying A2058 cell response to α2β1-integrin ligation is neither necessary nor sufficient and that elevated [Ca2+]i downregulates cell motility via a calcineurin-mediated mechanism in A2058 cell chemotaxis to CIV.

AB - We have investigated cellular Ca2+ regulation during A2058 human melanoma cell chemotaxis to type IV collagen (CIV). We have identified α2β1-integrin as the primary mediator of A2058 cell response to CIV in vitro. Integrin ligation initiated a characteristic intracellular Ca2+ concentration ([Ca2+]i) response consisting of an internal release and a receptor-mediated Ca2+ entry. Thapsigargin (TG) pretreatment drained overlapping and CIV-inducible internal Ca2+ stores while initiating a store-operated Ca2+ release (SOCR). CIV-mediated Ca2+ entry was additive to TG-SOCR, suggesting an independent signaling mechanism. Similarly, ionophore application in a basal medium containing Ca2+ initiated a sustained influx. Elevated [Ca2+]i from TG-SOCR or ionophore significantly attenuated cell migration to CIV by recruiting the Ca2+/calcineurin-mediated signaling pathway. Furthermore, low [Ca2+]i induced by EGTA application in the presence of ionophore fully restored cell motility to CIV. Together, these results suggest that [Ca2+]i signaling accompanying A2058 cell response to α2β1-integrin ligation is neither necessary nor sufficient and that elevated [Ca2+]i downregulates cell motility via a calcineurin-mediated mechanism in A2058 cell chemotaxis to CIV.

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