Effect of tertiary amine local anesthetics on the blood-borne implantation and cell surface properties of metastatic mouse melanoma cells

G. L. Nicolson, I. J. Fidler, George Poste

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Tertiary amine local anesthetics, such as dibucaine and tetracaine, have been found to reversibly modify the blood-borne implantation and experimental metastatic properties of B16 melanoma cells in syngeneic C57BL/6 mice. Local anesthetic treatment in vitro of low (B16-F1) and high (B16-F10) lung-colonizing melanoma variants reduced significantly their abilities to form lung tumor colonies, but the cells recovered their original in vivo colonizing properties within several hours after drug removal. Low drug concentrations (0.5 mM tetracaine) that altered the metastatic properties of these cells did not modify cell plating efficiencies or tumor growth rates at subcutaneous sites. With the use of [125I]-5-iodo-2'-deoxyuridine-labeled B16 cells, the kinetic distributions of viable tumor cells in mice were also shown to be altered. Fewer cells were initially localized and retained in the lungs, and more cells reached extrapulmonary sites. Local anesthetics modified B16 cell morphology, inducing cell rounding and loss of microvilli. These effects occurred concomitant with alterations in microfilament organization. Anesthetic-treated cells also exhibited decreased cell-adhesion characteristics in both homotypic and heterotypic (endothelial and subendothelial matrix) cell-adhesion assays. Despite these changes, cell surface lactoperoxidase-catalyzed iodination of external proteins and labeling of cellular glycoproteins on polyacrylamide gels with 125I-labeled lectins did not reveal differences in the displays or quantities of cell surface glycoproteins after drug treatment. The data are consistent with the idea that reversible disruptions in transmembrane cytoskeletal control induced by local anesthetics result in alterations in cell shape, loss of stable adhesive interactions, and a decrease in blood-borne arrest and metastatic properties.

Original languageEnglish (US)
Pages (from-to)511-519
Number of pages9
JournalJournal of the National Cancer Institute
Volume76
Issue number3
StatePublished - 1986
Externally publishedYes

Fingerprint

Surface Properties
Local Anesthetics
Amines
Melanoma
Tetracaine
Lung
Dibucaine
Cell-Matrix Junctions
Pharmaceutical Preparations
Idoxuridine
Lactoperoxidase
Neoplasms
Experimental Melanomas
Cell Shape
Halogenation
Membrane Glycoproteins
Microvilli
Actin Cytoskeleton
Inbred C57BL Mouse
Lectins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{7127e351e1ae4b14b2cbbedd4f3b34be,
title = "Effect of tertiary amine local anesthetics on the blood-borne implantation and cell surface properties of metastatic mouse melanoma cells",
abstract = "Tertiary amine local anesthetics, such as dibucaine and tetracaine, have been found to reversibly modify the blood-borne implantation and experimental metastatic properties of B16 melanoma cells in syngeneic C57BL/6 mice. Local anesthetic treatment in vitro of low (B16-F1) and high (B16-F10) lung-colonizing melanoma variants reduced significantly their abilities to form lung tumor colonies, but the cells recovered their original in vivo colonizing properties within several hours after drug removal. Low drug concentrations (0.5 mM tetracaine) that altered the metastatic properties of these cells did not modify cell plating efficiencies or tumor growth rates at subcutaneous sites. With the use of [125I]-5-iodo-2'-deoxyuridine-labeled B16 cells, the kinetic distributions of viable tumor cells in mice were also shown to be altered. Fewer cells were initially localized and retained in the lungs, and more cells reached extrapulmonary sites. Local anesthetics modified B16 cell morphology, inducing cell rounding and loss of microvilli. These effects occurred concomitant with alterations in microfilament organization. Anesthetic-treated cells also exhibited decreased cell-adhesion characteristics in both homotypic and heterotypic (endothelial and subendothelial matrix) cell-adhesion assays. Despite these changes, cell surface lactoperoxidase-catalyzed iodination of external proteins and labeling of cellular glycoproteins on polyacrylamide gels with 125I-labeled lectins did not reveal differences in the displays or quantities of cell surface glycoproteins after drug treatment. The data are consistent with the idea that reversible disruptions in transmembrane cytoskeletal control induced by local anesthetics result in alterations in cell shape, loss of stable adhesive interactions, and a decrease in blood-borne arrest and metastatic properties.",
author = "Nicolson, {G. L.} and Fidler, {I. J.} and George Poste",
year = "1986",
language = "English (US)",
volume = "76",
pages = "511--519",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - Effect of tertiary amine local anesthetics on the blood-borne implantation and cell surface properties of metastatic mouse melanoma cells

AU - Nicolson, G. L.

AU - Fidler, I. J.

AU - Poste, George

PY - 1986

Y1 - 1986

N2 - Tertiary amine local anesthetics, such as dibucaine and tetracaine, have been found to reversibly modify the blood-borne implantation and experimental metastatic properties of B16 melanoma cells in syngeneic C57BL/6 mice. Local anesthetic treatment in vitro of low (B16-F1) and high (B16-F10) lung-colonizing melanoma variants reduced significantly their abilities to form lung tumor colonies, but the cells recovered their original in vivo colonizing properties within several hours after drug removal. Low drug concentrations (0.5 mM tetracaine) that altered the metastatic properties of these cells did not modify cell plating efficiencies or tumor growth rates at subcutaneous sites. With the use of [125I]-5-iodo-2'-deoxyuridine-labeled B16 cells, the kinetic distributions of viable tumor cells in mice were also shown to be altered. Fewer cells were initially localized and retained in the lungs, and more cells reached extrapulmonary sites. Local anesthetics modified B16 cell morphology, inducing cell rounding and loss of microvilli. These effects occurred concomitant with alterations in microfilament organization. Anesthetic-treated cells also exhibited decreased cell-adhesion characteristics in both homotypic and heterotypic (endothelial and subendothelial matrix) cell-adhesion assays. Despite these changes, cell surface lactoperoxidase-catalyzed iodination of external proteins and labeling of cellular glycoproteins on polyacrylamide gels with 125I-labeled lectins did not reveal differences in the displays or quantities of cell surface glycoproteins after drug treatment. The data are consistent with the idea that reversible disruptions in transmembrane cytoskeletal control induced by local anesthetics result in alterations in cell shape, loss of stable adhesive interactions, and a decrease in blood-borne arrest and metastatic properties.

AB - Tertiary amine local anesthetics, such as dibucaine and tetracaine, have been found to reversibly modify the blood-borne implantation and experimental metastatic properties of B16 melanoma cells in syngeneic C57BL/6 mice. Local anesthetic treatment in vitro of low (B16-F1) and high (B16-F10) lung-colonizing melanoma variants reduced significantly their abilities to form lung tumor colonies, but the cells recovered their original in vivo colonizing properties within several hours after drug removal. Low drug concentrations (0.5 mM tetracaine) that altered the metastatic properties of these cells did not modify cell plating efficiencies or tumor growth rates at subcutaneous sites. With the use of [125I]-5-iodo-2'-deoxyuridine-labeled B16 cells, the kinetic distributions of viable tumor cells in mice were also shown to be altered. Fewer cells were initially localized and retained in the lungs, and more cells reached extrapulmonary sites. Local anesthetics modified B16 cell morphology, inducing cell rounding and loss of microvilli. These effects occurred concomitant with alterations in microfilament organization. Anesthetic-treated cells also exhibited decreased cell-adhesion characteristics in both homotypic and heterotypic (endothelial and subendothelial matrix) cell-adhesion assays. Despite these changes, cell surface lactoperoxidase-catalyzed iodination of external proteins and labeling of cellular glycoproteins on polyacrylamide gels with 125I-labeled lectins did not reveal differences in the displays or quantities of cell surface glycoproteins after drug treatment. The data are consistent with the idea that reversible disruptions in transmembrane cytoskeletal control induced by local anesthetics result in alterations in cell shape, loss of stable adhesive interactions, and a decrease in blood-borne arrest and metastatic properties.

UR - http://www.scopus.com/inward/record.url?scp=0022560011&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022560011&partnerID=8YFLogxK

M3 - Article

C2 - 3456465

AN - SCOPUS:0022560011

VL - 76

SP - 511

EP - 519

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 3

ER -