Different camptothecin sensitivities in subpopulations of colon cancer cells correlate with expression of different phospho-isoforms of topoisomerase i with different activities

Cinzia Tesauro; Josephine Geertsen Keller; Irina Gromova; Pavel Gromov; Rikke Frøhlich; Jens Uldum Erlandsen; Anni H. Andersen; Magnus Stougaard; Birgitta R. Knudsen

doi:10.3390/cancers12051240

Different camptothecin sensitivities in subpopulations of colon cancer cells correlate with expression of different phospho-isoforms of topoisomerase i with different activities

Cinzia Tesauro, Josephine Geertsen Keller, Irina Gromova, Pavel Gromov, Rikke Frøhlich, Jens Uldum Erlandsen, Anni H. Andersen, Magnus Stougaard, Birgitta R. Knudsen^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

11 Citationer (Scopus)

Abstract

The heterogeneity of tumor cells and the potential existence of rare cells with reduced chemotherapeutic response is expected to play a pivotal role in the development of drug resistant cancers. Herein, we utilized the colon cancer cell lines, Caco2 and DLD1, to investigate heterogeneity of topoisomerase 1 (TOP1) activity in different cell subpopulations, and the consequences for the chemotherapeutic response towards the TOP1 targeting drug, camptothecin. The cell lines consisted of two subpopulations: one (the stem-cell-like cells) divided asymmetrically, was camptothecin resistant, had a differently phosphorylated TOP1 and a lower Casein Kinase II (CKII) activity than the camptothecin sensitive non-stem-cell-like cells. The tumor suppressor p14ARF had a different effect in the two cell subpopulations. In the stem-cell-like cells, p14ARF suppressed TOP1 activity and downregulation of this factor increased the sensitivity towards camptothecin. It had the opposite effect in non-stem-cell-like cells. Since it is only the stem-cell-like cells that have tumorigenic activity our results point towards new considerations for future cancer therapy. Moreover, the data underscore the importance of considering cell-to-cell variations in the analysis of molecular processes in cell lines.

Originalsprog	Engelsk
Artikelnummer	1240
Tidsskrift	Cancers
Vol/bind	12
Nummer	5
Antal sider	21
ISSN	2072-6694
DOI	https://doi.org/10.3390/cancers12051240
Status	Udgivet - maj 2020

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10.3390/cancers12051240

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Citationsformater

Tesauro, C., Keller, J. G., Gromova, I., Gromov, P., Frøhlich, R., Erlandsen, J. U., Andersen, A. H., Stougaard, M., & Knudsen, B. R. (2020). Different camptothecin sensitivities in subpopulations of colon cancer cells correlate with expression of different phospho-isoforms of topoisomerase i with different activities. Cancers, 12(5), Artikel 1240. https://doi.org/10.3390/cancers12051240

@article{35d35dcd343145ac93532fd63b712c34,

title = "Different camptothecin sensitivities in subpopulations of colon cancer cells correlate with expression of different phospho-isoforms of topoisomerase i with different activities",

abstract = "The heterogeneity of tumor cells and the potential existence of rare cells with reduced chemotherapeutic response is expected to play a pivotal role in the development of drug resistant cancers. Herein, we utilized the colon cancer cell lines, Caco2 and DLD1, to investigate heterogeneity of topoisomerase 1 (TOP1) activity in different cell subpopulations, and the consequences for the chemotherapeutic response towards the TOP1 targeting drug, camptothecin. The cell lines consisted of two subpopulations: one (the stem-cell-like cells) divided asymmetrically, was camptothecin resistant, had a differently phosphorylated TOP1 and a lower Casein Kinase II (CKII) activity than the camptothecin sensitive non-stem-cell-like cells. The tumor suppressor p14ARF had a different effect in the two cell subpopulations. In the stem-cell-like cells, p14ARF suppressed TOP1 activity and downregulation of this factor increased the sensitivity towards camptothecin. It had the opposite effect in non-stem-cell-like cells. Since it is only the stem-cell-like cells that have tumorigenic activity our results point towards new considerations for future cancer therapy. Moreover, the data underscore the importance of considering cell-to-cell variations in the analysis of molecular processes in cell lines.",

keywords = "Camptothecin, Cell heterogeneity, Colon cancer, Phosphorylation, Topoisomerase 1",

author = "Cinzia Tesauro and Keller, {Josephine Geertsen} and Irina Gromova and Pavel Gromov and Rikke Fr{\o}hlich and Erlandsen, {Jens Uldum} and Andersen, {Anni H.} and Magnus Stougaard and Knudsen, {Birgitta R.}",

year = "2020",

month = may,

doi = "10.3390/cancers12051240",

language = "English",

volume = "12",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "5",

}

Tesauro, C , Keller, JG, Gromova, I, Gromov, P, Frøhlich, R , Erlandsen, JU , Andersen, AH , Stougaard, M & Knudsen, BR 2020, 'Different camptothecin sensitivities in subpopulations of colon cancer cells correlate with expression of different phospho-isoforms of topoisomerase i with different activities', Cancers, bind 12, nr. 5, 1240. https://doi.org/10.3390/cancers12051240

Different camptothecin sensitivities in subpopulations of colon cancer cells correlate with expression of different phospho-isoforms of topoisomerase i with different activities. / Tesauro, Cinzia ; Keller, Josephine Geertsen; Gromova, Irina et al.
I: Cancers, Bind 12, Nr. 5, 1240, 05.2020.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Different camptothecin sensitivities in subpopulations of colon cancer cells correlate with expression of different phospho-isoforms of topoisomerase i with different activities

AU - Tesauro, Cinzia

AU - Keller, Josephine Geertsen

AU - Gromova, Irina

AU - Gromov, Pavel

AU - Frøhlich, Rikke

AU - Erlandsen, Jens Uldum

AU - Andersen, Anni H.

AU - Stougaard, Magnus

AU - Knudsen, Birgitta R.

PY - 2020/5

Y1 - 2020/5

N2 - The heterogeneity of tumor cells and the potential existence of rare cells with reduced chemotherapeutic response is expected to play a pivotal role in the development of drug resistant cancers. Herein, we utilized the colon cancer cell lines, Caco2 and DLD1, to investigate heterogeneity of topoisomerase 1 (TOP1) activity in different cell subpopulations, and the consequences for the chemotherapeutic response towards the TOP1 targeting drug, camptothecin. The cell lines consisted of two subpopulations: one (the stem-cell-like cells) divided asymmetrically, was camptothecin resistant, had a differently phosphorylated TOP1 and a lower Casein Kinase II (CKII) activity than the camptothecin sensitive non-stem-cell-like cells. The tumor suppressor p14ARF had a different effect in the two cell subpopulations. In the stem-cell-like cells, p14ARF suppressed TOP1 activity and downregulation of this factor increased the sensitivity towards camptothecin. It had the opposite effect in non-stem-cell-like cells. Since it is only the stem-cell-like cells that have tumorigenic activity our results point towards new considerations for future cancer therapy. Moreover, the data underscore the importance of considering cell-to-cell variations in the analysis of molecular processes in cell lines.

AB - The heterogeneity of tumor cells and the potential existence of rare cells with reduced chemotherapeutic response is expected to play a pivotal role in the development of drug resistant cancers. Herein, we utilized the colon cancer cell lines, Caco2 and DLD1, to investigate heterogeneity of topoisomerase 1 (TOP1) activity in different cell subpopulations, and the consequences for the chemotherapeutic response towards the TOP1 targeting drug, camptothecin. The cell lines consisted of two subpopulations: one (the stem-cell-like cells) divided asymmetrically, was camptothecin resistant, had a differently phosphorylated TOP1 and a lower Casein Kinase II (CKII) activity than the camptothecin sensitive non-stem-cell-like cells. The tumor suppressor p14ARF had a different effect in the two cell subpopulations. In the stem-cell-like cells, p14ARF suppressed TOP1 activity and downregulation of this factor increased the sensitivity towards camptothecin. It had the opposite effect in non-stem-cell-like cells. Since it is only the stem-cell-like cells that have tumorigenic activity our results point towards new considerations for future cancer therapy. Moreover, the data underscore the importance of considering cell-to-cell variations in the analysis of molecular processes in cell lines.

KW - Camptothecin

KW - Cell heterogeneity

KW - Colon cancer

KW - Phosphorylation

KW - Topoisomerase 1

UR - http://www.scopus.com/inward/record.url?scp=85085109983&partnerID=8YFLogxK

U2 - 10.3390/cancers12051240

DO - 10.3390/cancers12051240

M3 - Journal article

C2 - 32423158

AN - SCOPUS:85085109983

SN - 2072-6694

VL - 12

JO - Cancers

JF - Cancers

IS - 5

M1 - 1240

ER -

Different camptothecin sensitivities in subpopulations of colon cancer cells correlate with expression of different phospho-isoforms of topoisomerase i with different activities

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