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 normal lung cells. Conclusions 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. Keywords: Cancer cells, chemotaxis, chemokinesis, motility, gene regulation.
Overall design
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.
J04423 E coli bioB gene biotin synthetase (-5, -M, -3 represent transcript regions 5 prime, Middle, and 3 prime respectively)
AFFX-BioB-M_at
-0.2
NC
0.5
J04423 E coli bioB gene biotin synthetase (-5, -M, -3 represent transcript regions 5 prime, Middle, and 3 prime respectively)
AFFX-BioB-3_at
-0.4
NC
0.5
J04423 E coli bioB gene biotin synthetase (-5, -M, -3 represent transcript regions 5 prime, Middle, and 3 prime respectively)
AFFX-BioC-5_at
-0.4
NC
0.5
J04423 E coli bioC protein (-5 and -3 represent transcript regions 5 prime and 3 prime respectively)
AFFX-BioC-3_at
-0.2
NC
0.5
J04423 E coli bioC protein (-5 and -3 represent transcript regions 5 prime and 3 prime respectively)
AFFX-BioDn-5_at
-0.3
NC
0.5
J04423 E coli bioD gene dethiobiotin synthetase (-5 and -3 represent transcript regions 5 prime and 3 prime respectively)
AFFX-BioDn-3_at
-0.7
NC
0.920927
J04423 E coli bioD gene dethiobiotin synthetase (-5 and -3 represent transcript regions 5 prime and 3 prime respectively)
AFFX-CreX-5_at
-0.3
NC
0.5
X03453 Bacteriophage P1 cre recombinase protein (-5 and -3 represent transcript regions 5 prime and 3 prime respectively)
AFFX-CreX-3_at
-0.5
NC
0.950863
X03453 Bacteriophage P1 cre recombinase protein (-5 and -3 represent transcript regions 5 prime and 3 prime respectively)
AFFX-DapX-5_at
-0.1
NC
0.255069
L38424 B subtilis dapB, jojF, jojG genes corresponding to nucleotides 1358-3197 of L38424 (-5, -M, -3 represent transcript regions 5 prime, Middle, and 3 prime respectively)
AFFX-DapX-M_at
-0.1
NC
0.5
L38424 B subtilis dapB, jojF, jojG genes corresponding to nucleotides 1358-3197 of L38424 (-5, -M, -3 represent transcript regions 5 prime, Middle, and 3 prime respectively)
AFFX-DapX-3_at
-0.5
NC
0.5
L38424 B subtilis dapB, jojF, jojG genes corresponding to nucleotides 1358-3197 of L38424 (-5, -M, -3 represent transcript regions 5 prime, Middle, and 3 prime respectively)
AFFX-LysX-5_at
-2.4
NC
0.793869
X17013 B subtilis lys gene for diaminopimelate decarboxylase corresponding to nucleotides 350-1345 of X17013 (-5, -M, -3 represent transcript regions 5 prime, Middle, and 3 prime respectively)
AFFX-LysX-M_at
0.9
NC
0.378604
X17013 B subtilis lys gene for diaminopimelate decarboxylase corresponding to nucleotides 350-1345 of X17013 (-5, -M, -3 represent transcript regions 5 prime, Middle, and 3 prime respectively)
AFFX-LysX-3_at
-0.6
NC
0.5
X17013 B subtilis lys gene for diaminopimelate decarboxylase corresponding to nucleotides 350-1345 of X17013 (-5, -M, -3 represent transcript regions 5 prime, Middle, and 3 prime respectively)
AFFX-PheX-5_at
-0.6
NC
0.600787
M24537B subtilis pheB, pheA genes corresponding to nucleotides 2017-3334 of M24537 (-5, -M, -3 represent transcript regions 5 prime, Middle, and 3 prime respectively)
AFFX-PheX-M_at
1.1
NC
0.5
M24537B subtilis pheB, pheA genes corresponding to nucleotides 2017-3334 of M24537 (-5, -M, -3 represent transcript regions 5 prime, Middle, and 3 prime respectively)
AFFX-PheX-3_at
0
NC
0.680982
M24537B subtilis pheB, pheA genes corresponding to nucleotides 2017-3334 of M24537 (-5, -M, -3 represent transcript regions 5 prime, Middle, and 3 prime respectively)
AFFX-ThrX-5_at
-1.9
NC
0.685767
X04603 B subtilis thrC, thrB genes corresponding to nucleotides 248-2229 of X04603 (-5, -M, -3 represent transcript regions 5 prime, Middle, and 3 prime respectively)
AFFX-ThrX-M_at
1.3
NC
0.5
X04603 B subtilis thrC, thrB genes corresponding to nucleotides 248-2229 of X04603 (-5, -M, -3 represent transcript regions 5 prime, Middle, and 3 prime respectively)
