Extracellular lipid-mediated signaling in tumor-cell activation and pseudopod protrusion

Louis Hodgson, Elise C. Kohn, Cheng Dong

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

We have pioneered an in vitro pseudopod-generation model wherein suspended tumor cells are stimulated to form pseudopods into glass micropipettes in response to soluble collagen type IV (CIV). Pertussis toxin and removing intracellular calcium were found previously to be inhibitory to that process. We now extend those observations to dissect the roles of transmembrane calcium influx and circulating fatty acids on pseudopod extension. Removal of fatty acids from BSA in basal media resulted in abrogation of pseudopod formation, while reconstitution of free fatty acids restored cell pseudopod protrusion. We thus hypothesized that fatty acids may provide necessary pseudopod stimulatory signals. Addition of lysophosphatidic acid (LPA) to the fatty acid-free CIV solution or in an opposite pipette without CIV permitted approximately 50% pseudopod recovery in all pipette directions in a dose-dependent fashion. Thapsigargin (TG), an agent that releases internal calcium stores and causes opening of store-operated calcium channels, restored pseudopod protrusion up to 80% in CIV with fatty acid-free albumin. [Ca2+](i) release was non-additive when cells were stimulated by TG and LPA, suggesting overlapping [Ca2+](i) stores. The combination of TG and LPA in fatty acid-free albumin fully restored the pseudopod response to CIV. Addition of EGTA to chelate stimulatory media calcium blocked the pseudopod response to CIV in the presence of fatty acids. This indicates that pseudopod protrusion requires transmembrane calcium entry. Thus, extracellular lipids and calcium mobilization are required to complement CIV in pseudopod protrusion from suspended cells. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)593-600
Number of pages8
JournalInternational Journal of Cancer
Volume88
Issue number4
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Pseudopodia
Collagen Type IV
Lipids
Neoplasms
Calcium
Nonesterified Fatty Acids
Thapsigargin
Fatty Acids
Albumins
Lipid Mobilization
Egtazic Acid
Pertussis Toxin
Calcium Channels
Glass

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Extracellular lipid-mediated signaling in tumor-cell activation and pseudopod protrusion. / Hodgson, Louis; Kohn, Elise C.; Dong, Cheng.

In: International Journal of Cancer, Vol. 88, No. 4, 2000, p. 593-600.

Research output: Contribution to journalArticle

@article{b31be2f51c80447998a67dd80249dc85,
title = "Extracellular lipid-mediated signaling in tumor-cell activation and pseudopod protrusion",
abstract = "We have pioneered an in vitro pseudopod-generation model wherein suspended tumor cells are stimulated to form pseudopods into glass micropipettes in response to soluble collagen type IV (CIV). Pertussis toxin and removing intracellular calcium were found previously to be inhibitory to that process. We now extend those observations to dissect the roles of transmembrane calcium influx and circulating fatty acids on pseudopod extension. Removal of fatty acids from BSA in basal media resulted in abrogation of pseudopod formation, while reconstitution of free fatty acids restored cell pseudopod protrusion. We thus hypothesized that fatty acids may provide necessary pseudopod stimulatory signals. Addition of lysophosphatidic acid (LPA) to the fatty acid-free CIV solution or in an opposite pipette without CIV permitted approximately 50{\%} pseudopod recovery in all pipette directions in a dose-dependent fashion. Thapsigargin (TG), an agent that releases internal calcium stores and causes opening of store-operated calcium channels, restored pseudopod protrusion up to 80{\%} in CIV with fatty acid-free albumin. [Ca2+](i) release was non-additive when cells were stimulated by TG and LPA, suggesting overlapping [Ca2+](i) stores. The combination of TG and LPA in fatty acid-free albumin fully restored the pseudopod response to CIV. Addition of EGTA to chelate stimulatory media calcium blocked the pseudopod response to CIV in the presence of fatty acids. This indicates that pseudopod protrusion requires transmembrane calcium entry. Thus, extracellular lipids and calcium mobilization are required to complement CIV in pseudopod protrusion from suspended cells. (C) 2000 Wiley-Liss, Inc.",
author = "Louis Hodgson and Kohn, {Elise C.} and Cheng Dong",
year = "2000",
doi = "10.1002/1097-0215(20001115)88:4<593::AID-IJC12>3.0.CO;2-O",
language = "English (US)",
volume = "88",
pages = "593--600",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Extracellular lipid-mediated signaling in tumor-cell activation and pseudopod protrusion

AU - Hodgson, Louis

AU - Kohn, Elise C.

AU - Dong, Cheng

PY - 2000

Y1 - 2000

N2 - We have pioneered an in vitro pseudopod-generation model wherein suspended tumor cells are stimulated to form pseudopods into glass micropipettes in response to soluble collagen type IV (CIV). Pertussis toxin and removing intracellular calcium were found previously to be inhibitory to that process. We now extend those observations to dissect the roles of transmembrane calcium influx and circulating fatty acids on pseudopod extension. Removal of fatty acids from BSA in basal media resulted in abrogation of pseudopod formation, while reconstitution of free fatty acids restored cell pseudopod protrusion. We thus hypothesized that fatty acids may provide necessary pseudopod stimulatory signals. Addition of lysophosphatidic acid (LPA) to the fatty acid-free CIV solution or in an opposite pipette without CIV permitted approximately 50% pseudopod recovery in all pipette directions in a dose-dependent fashion. Thapsigargin (TG), an agent that releases internal calcium stores and causes opening of store-operated calcium channels, restored pseudopod protrusion up to 80% in CIV with fatty acid-free albumin. [Ca2+](i) release was non-additive when cells were stimulated by TG and LPA, suggesting overlapping [Ca2+](i) stores. The combination of TG and LPA in fatty acid-free albumin fully restored the pseudopod response to CIV. Addition of EGTA to chelate stimulatory media calcium blocked the pseudopod response to CIV in the presence of fatty acids. This indicates that pseudopod protrusion requires transmembrane calcium entry. Thus, extracellular lipids and calcium mobilization are required to complement CIV in pseudopod protrusion from suspended cells. (C) 2000 Wiley-Liss, Inc.

AB - We have pioneered an in vitro pseudopod-generation model wherein suspended tumor cells are stimulated to form pseudopods into glass micropipettes in response to soluble collagen type IV (CIV). Pertussis toxin and removing intracellular calcium were found previously to be inhibitory to that process. We now extend those observations to dissect the roles of transmembrane calcium influx and circulating fatty acids on pseudopod extension. Removal of fatty acids from BSA in basal media resulted in abrogation of pseudopod formation, while reconstitution of free fatty acids restored cell pseudopod protrusion. We thus hypothesized that fatty acids may provide necessary pseudopod stimulatory signals. Addition of lysophosphatidic acid (LPA) to the fatty acid-free CIV solution or in an opposite pipette without CIV permitted approximately 50% pseudopod recovery in all pipette directions in a dose-dependent fashion. Thapsigargin (TG), an agent that releases internal calcium stores and causes opening of store-operated calcium channels, restored pseudopod protrusion up to 80% in CIV with fatty acid-free albumin. [Ca2+](i) release was non-additive when cells were stimulated by TG and LPA, suggesting overlapping [Ca2+](i) stores. The combination of TG and LPA in fatty acid-free albumin fully restored the pseudopod response to CIV. Addition of EGTA to chelate stimulatory media calcium blocked the pseudopod response to CIV in the presence of fatty acids. This indicates that pseudopod protrusion requires transmembrane calcium entry. Thus, extracellular lipids and calcium mobilization are required to complement CIV in pseudopod protrusion from suspended cells. (C) 2000 Wiley-Liss, Inc.

UR - http://www.scopus.com/inward/record.url?scp=0033766982&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033766982&partnerID=8YFLogxK

U2 - 10.1002/1097-0215(20001115)88:4<593::AID-IJC12>3.0.CO;2-O

DO - 10.1002/1097-0215(20001115)88:4<593::AID-IJC12>3.0.CO;2-O

M3 - Article

C2 - 11058876

AN - SCOPUS:0033766982

VL - 88

SP - 593

EP - 600

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 4

ER -