Effects of transforming growth factor-β1 on human pulmonary adenocarcinoma cell adhesion, motility, and invasion in vitro

Daniel L. Mooradian, James B. McCarthy, Krishna V Komanduri, Leo T. Furcht

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Background: Transforming growth factor-β1 (TGF-β1), a potent growth modulator produced by a variety of tumor cells, as well as by platelets, has pleiotropic effects on cell-extracellular matrix interactions and may influence tumor cell invasion and metastasis. Purpose: Our purpose was to characterize the effects of TGF-β1 on the adhesion, motility, and invasiveness of a metastatic human pulmonary carcinoma (A549 cell line) in vitro. Methods: A549 cells were seeded onto type I collagen gels, and invasion over a 9-day period was measured in the presence or absence of TGF-β1 (0.1-10 ng/mL). In addition, cell adhesion to substrata coated with type I collagen (1-100 nM) as well as haptotactic migration through filters coated with type I collagen (100 μg/mL) were measured following a 24-hour treatment with TGF-β1 (1-10 ng/mL). Results: TGF-β1 stimulated the invasion of A549 cells into type I collagen gels in a dose-dependent manner. Both the number of cells entering the gel and the depth of invasion into the gel were increased. In addition, the effects of TGF-β1 were blocked in a dose-dependent manner by a purified polyclonal IgG against TGF-β1 but not by normal rabbit IgG. A549 cell invasion was accompanied by dramatic changes in A549 cell morphology that included the appearance of numerous long pseudopodia, consistent with a change in the motile behavior of these cells. TGF-β1 stimulated by approximately fourfold the haptotactic migration of A549 cells on polycarbonate filters coated with type I collagen. The TGF-β1-mediated increase in invasion and motility was accompanied by a fourfold increase in A549 cell adhesion to type I collagen. Conclusions: The results suggest that TGF-β1 can influence cellular recognition of extracellular matrix components and can modulate cellular adhesion and migration on these components, leading to increased invasive potential. Implications: Given the wide-spread tissue distribution of TGF-β1 and its secretion by a variety of tumor cells as well as by platelets, TGF-β1 may be an important autocrine-paracrine regulator of the invasive phenotype in vivo.

Original languageEnglish
Pages (from-to)523-527
Number of pages5
JournalJournal of the National Cancer Institute
Volume84
Issue number7
StatePublished - Apr 1 1992
Externally publishedYes

Fingerprint

Cell Adhesion
Motility
Growth Factors
Cell adhesion
Invasion
Transforming Growth Factors
Cell Movement
Collagen
Collagen Type I
Cell
Cells
Gels
Migration
polycarbonate
Tumors
Tumor
Platelets
Adhesion
Extracellular Matrix
Human

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Radiology Nuclear Medicine and imaging

Cite this

Effects of transforming growth factor-β1 on human pulmonary adenocarcinoma cell adhesion, motility, and invasion in vitro. / Mooradian, Daniel L.; McCarthy, James B.; Komanduri, Krishna V; Furcht, Leo T.

In: Journal of the National Cancer Institute, Vol. 84, No. 7, 01.04.1992, p. 523-527.

Research output: Contribution to journalArticle

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