Rapid chemokinetic movement and the invasive potential of lung cancer cells; a functional molecular study

Sandra Y Y Fok, Jeffrey S. Rubin, Fiona Pixley, John S. Condeelis, Filip Braet, Lilian L. Soon

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Non-small cell lung cancer is the most common cause of early casualty from malignant disease in western countries. The heterogeneous nature of these cells has been identified by histochemical and microarray biomarker analyses. Unfortunately, the morphological, molecular and biological variation within cell lines used as models for invasion and metastasis are not well understood. In this study, we test the hypothesis that heterogeneous cancer cells exhibit variable motility responses such as chemokinesis and chemotaxis that can be characterized molecularly. Methods: A subpopulation of H460 lung cancer cells called KINE that migrated under chemokinetic (no gradient) conditions was harvested from Boyden chambers and cultured. Time-lapsed microscopy, immunofluorescence microscopy and microarray analyses were then carried out comparing chemokinetic KINE cells with the unselected CON cell population. Results: Time-lapsed microscopy and analysis showed that KINE cells moved faster but less directionally than the unselected control population (CON), confirming their chemokinetic character. Of note was that chemokinetic KINE cells also chemotaxed efficiently. KINE cells were less adhesive to substrate than CON cells and demonstrated loss of mature focal adhesions at the leading edge and the presence of non-focalized cortical actin. These characteristics are common in highly motile amoeboid cells that may favour faster motility speeds. KINE cells were also significantly more invasive compared to CON. Gene array studies and real-time PCR showed the downregulation of a gene called, ROM, in highly chemokinetic KINE compared to mainly chemotactic CON cells. ROM was also reduced in expression in a panel of lung cancer cell lines compared to normal lung cells. Conclusion: This study shows that cancer cells that are efficient in both chemokinesis and chemotaxis demonstrate high invasion levels. These cells possess different morphological, cytoskeletal and adhesive properties from another population that are only efficient at chemotaxis, indicating a loss in polarity. Understanding the regulation of polarity in the context of cell motility is important in order to improve control and inhibition of invasion and metastasis.

Original languageEnglish (US)
Article number151
JournalBMC Cancer
Volume6
DOIs
StatePublished - Jun 7 2006

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Lung Neoplasms
Population
Chemotaxis
Microarray Analysis
Adhesives
Microscopy
Neoplasm Metastasis
Cell Line
Focal Adhesions
Fluorescence Microscopy
Non-Small Cell Lung Carcinoma
Genes
Cell Movement
Actins
Real-Time Polymerase Chain Reaction
Neoplasms
Down-Regulation
Biomarkers

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Rapid chemokinetic movement and the invasive potential of lung cancer cells; a functional molecular study. / Fok, Sandra Y Y; Rubin, Jeffrey S.; Pixley, Fiona; Condeelis, John S.; Braet, Filip; Soon, Lilian L.

In: BMC Cancer, Vol. 6, 151, 07.06.2006.

Research output: Contribution to journalArticle

Fok, Sandra Y Y ; Rubin, Jeffrey S. ; Pixley, Fiona ; Condeelis, John S. ; Braet, Filip ; Soon, Lilian L. / Rapid chemokinetic movement and the invasive potential of lung cancer cells; a functional molecular study. In: BMC Cancer. 2006 ; Vol. 6.
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abstract = "Background: Non-small cell lung cancer is the most common cause of early casualty from malignant disease in western countries. The heterogeneous nature of these cells has been identified by histochemical and microarray biomarker analyses. Unfortunately, the morphological, molecular and biological variation within cell lines used as models for invasion and metastasis are not well understood. In this study, we test the hypothesis that heterogeneous cancer cells exhibit variable motility responses such as chemokinesis and chemotaxis that can be characterized molecularly. Methods: A subpopulation of H460 lung cancer cells called KINE that migrated under chemokinetic (no gradient) conditions was harvested from Boyden chambers and cultured. Time-lapsed microscopy, immunofluorescence microscopy and microarray analyses were then carried out comparing chemokinetic KINE cells with the unselected CON cell population. Results: Time-lapsed microscopy and analysis showed that KINE cells moved faster but less directionally than the unselected control population (CON), confirming their chemokinetic character. Of note was that chemokinetic KINE cells also chemotaxed efficiently. KINE cells were less adhesive to substrate than CON cells and demonstrated loss of mature focal adhesions at the leading edge and the presence of non-focalized cortical actin. These characteristics are common in highly motile amoeboid cells that may favour faster motility speeds. KINE cells were also significantly more invasive compared to CON. Gene array studies and real-time PCR showed the downregulation of a gene called, ROM, in highly chemokinetic KINE compared to mainly chemotactic CON cells. ROM was also reduced in expression in a panel of lung cancer cell lines compared to normal lung cells. Conclusion: This study shows that cancer cells that are efficient in both chemokinesis and chemotaxis demonstrate high invasion levels. These cells possess different morphological, cytoskeletal and adhesive properties from another population that are only efficient at chemotaxis, indicating a loss in polarity. Understanding the regulation of polarity in the context of cell motility is important in order to improve control and inhibition of invasion and metastasis.",
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