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Receptor tyrosine kinase expression of circulating tumor cells in small cell lung cancer.

Hamilton G, Rath B, Klameth L, Hochmair M - Oncoscience (2015)

Bottom Line: The cell biological mechanisms underlying metastasis and drug resistance are not clear.The CTC cell line BHGc10 was found to exhibit increased expression of RYK, AXL, Tie-1, Dtk, ROR1/2, several ephrins (Eph) and FGF/EGF receptors compared to SCLC26A.All of these RTKs have been associated with cell motility, invasion and poor prognosis in diverse cancer entities without knowledge of their association with CTCs.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Boltzmann Cluster of Translational Oncology, Vienna, Austria.

ABSTRACT
Small cell lung cancer (SCLC) has a poor prognosis and is found disseminated at first presentation in the majority of cases. The cell biological mechanisms underlying metastasis and drug resistance are not clear. SCLC is characterized by high numbers of circulating tumor cells (CTCs) and we were able to expand several CTC lines ex vivo and to relate chitinase-3-like-1/YKL-40 (CHI3L1) as marker. Availability of expanded SCLC CTC cells allowed for a screening of receptor tyrosine kinases (RTKs) expressed. The metastatic CHI3L1-negative SCLC cell line SCLC26A, established from a pleural effusion was used for comparison. The CTC cell line BHGc10 was found to exhibit increased expression of RYK, AXL, Tie-1, Dtk, ROR1/2, several ephrins (Eph) and FGF/EGF receptors compared to SCLC26A. All of these RTKs have been associated with cell motility, invasion and poor prognosis in diverse cancer entities without knowledge of their association with CTCs. The identification of RYK, AXL and ROR1/2 as pseudokinases, lacking activity, seems to be related to the observed failure of RTK inhibitors in SCLC. These kinases are involved in the noncanonical WNT pathway and their expression in SCLC CTCs represents a cancer stem cell-like phenotype.

No MeSH data available.


Related in: MedlinePlus

Expression of selected RTKs in SCLC26A cellsRTKs expressed in SCLC26A cAQ1ells which correspond to RTKs overexpressed in BHGc10 CTC cells are shown (mean ± SD, arbitrary intensity units).
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Figure 1: Expression of selected RTKs in SCLC26A cellsRTKs expressed in SCLC26A cAQ1ells which correspond to RTKs overexpressed in BHGc10 CTC cells are shown (mean ± SD, arbitrary intensity units).

Mentions: Expression of RTKs was detected on the Western blot arrays for SCLC26A and BHGc10 SCLC CTC cells, respectively. Figure 1 shows the control RTKs of the local metastatic SCLC26A cell line to be compared with those of the BHGc10 SCLC CTC line, isolated from peripheral blood. SCLC26A relies on EGFR, InsulinR and FGFRs for growth and expresses several kinases, including RYK, ROR1/2 and members of the ephrin family.


Receptor tyrosine kinase expression of circulating tumor cells in small cell lung cancer.

Hamilton G, Rath B, Klameth L, Hochmair M - Oncoscience (2015)

Expression of selected RTKs in SCLC26A cellsRTKs expressed in SCLC26A cAQ1ells which correspond to RTKs overexpressed in BHGc10 CTC cells are shown (mean ± SD, arbitrary intensity units).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4549360&req=5

Figure 1: Expression of selected RTKs in SCLC26A cellsRTKs expressed in SCLC26A cAQ1ells which correspond to RTKs overexpressed in BHGc10 CTC cells are shown (mean ± SD, arbitrary intensity units).
Mentions: Expression of RTKs was detected on the Western blot arrays for SCLC26A and BHGc10 SCLC CTC cells, respectively. Figure 1 shows the control RTKs of the local metastatic SCLC26A cell line to be compared with those of the BHGc10 SCLC CTC line, isolated from peripheral blood. SCLC26A relies on EGFR, InsulinR and FGFRs for growth and expresses several kinases, including RYK, ROR1/2 and members of the ephrin family.

Bottom Line: The cell biological mechanisms underlying metastasis and drug resistance are not clear.The CTC cell line BHGc10 was found to exhibit increased expression of RYK, AXL, Tie-1, Dtk, ROR1/2, several ephrins (Eph) and FGF/EGF receptors compared to SCLC26A.All of these RTKs have been associated with cell motility, invasion and poor prognosis in diverse cancer entities without knowledge of their association with CTCs.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Boltzmann Cluster of Translational Oncology, Vienna, Austria.

ABSTRACT
Small cell lung cancer (SCLC) has a poor prognosis and is found disseminated at first presentation in the majority of cases. The cell biological mechanisms underlying metastasis and drug resistance are not clear. SCLC is characterized by high numbers of circulating tumor cells (CTCs) and we were able to expand several CTC lines ex vivo and to relate chitinase-3-like-1/YKL-40 (CHI3L1) as marker. Availability of expanded SCLC CTC cells allowed for a screening of receptor tyrosine kinases (RTKs) expressed. The metastatic CHI3L1-negative SCLC cell line SCLC26A, established from a pleural effusion was used for comparison. The CTC cell line BHGc10 was found to exhibit increased expression of RYK, AXL, Tie-1, Dtk, ROR1/2, several ephrins (Eph) and FGF/EGF receptors compared to SCLC26A. All of these RTKs have been associated with cell motility, invasion and poor prognosis in diverse cancer entities without knowledge of their association with CTCs. The identification of RYK, AXL and ROR1/2 as pseudokinases, lacking activity, seems to be related to the observed failure of RTK inhibitors in SCLC. These kinases are involved in the noncanonical WNT pathway and their expression in SCLC CTCs represents a cancer stem cell-like phenotype.

No MeSH data available.


Related in: MedlinePlus