Small cell lung cancer: model of circulating tumor cell tumorospheres in chemoresistance

Abstract Small cell lung cancer (SCLC) represents 15% of lung cancers and is characterized by early dissemination, development of chemoresistance and a poor prognosis. A host of diverse drugs failed invariably and its mechanisms of global chemoresistance have not been characterized so far. SCLC repr...

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Autores principales:	Lukas Klameth, Barbara Rath, Maximilian Hochmaier, Doris Moser, Marlene Redl, Felicitas Mungenast, Katharina Gelles, Ernst Ulsperger, Robert Zeillinger, Gerhard Hamilton
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a2cf85fb0b7042ae8e2904ae222c0bb0
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spelling	oai:doaj.org-article:a2cf85fb0b7042ae8e2904ae222c0bb02021-12-02T11:40:51ZSmall cell lung cancer: model of circulating tumor cell tumorospheres in chemoresistance10.1038/s41598-017-05562-z2045-2322https://doaj.org/article/a2cf85fb0b7042ae8e2904ae222c0bb02017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05562-zhttps://doaj.org/toc/2045-2322Abstract Small cell lung cancer (SCLC) represents 15% of lung cancers and is characterized by early dissemination, development of chemoresistance and a poor prognosis. A host of diverse drugs failed invariably and its mechanisms of global chemoresistance have not been characterized so far. SCLC represents the prototype of an aggressive and highly metastatic tumor which is ultimately refractory to any treatment. High numbers of circulating tumor cells (CTCs) allowed us to establish 5 CTC cell lines (BHGc7, 10, 16, 26 and UHGc5) from patients with recurrent SCLC. These cell lines exhibit the typical SCLC markers and CTCs of all patients developed spontaneously large multicellular aggregates, termed tumorospheres. Ki67 and carbonic anhydrase 9 (CAIX) staining of tumorosphere sections revealed quiescent and hypoxic cells, respectively. Accordingly, comparison of the chemosensitivity of CTC single cell suspensions with tumorospheres demonstrated increased resistance of the clusters against chemotherapeutics commonly used for treatment of SCLC. Therefore, global chemoresistance of relapsing SCLC seems to rely on formation of large tumorospheres which reveal limited accessibility, lower growth fraction and hypoxic conditions. Since similar tumor spheroids were found in other tumor types, SCLC seems to represent a unique tumor model to study the association of CTCs, metastasis and drug resistance.Lukas KlamethBarbara RathMaximilian HochmaierDoris MoserMarlene RedlFelicitas MungenastKatharina GellesErnst UlspergerRobert ZeillingerGerhard HamiltonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lukas Klameth Barbara Rath Maximilian Hochmaier Doris Moser Marlene Redl Felicitas Mungenast Katharina Gelles Ernst Ulsperger Robert Zeillinger Gerhard Hamilton Small cell lung cancer: model of circulating tumor cell tumorospheres in chemoresistance
description	Abstract Small cell lung cancer (SCLC) represents 15% of lung cancers and is characterized by early dissemination, development of chemoresistance and a poor prognosis. A host of diverse drugs failed invariably and its mechanisms of global chemoresistance have not been characterized so far. SCLC represents the prototype of an aggressive and highly metastatic tumor which is ultimately refractory to any treatment. High numbers of circulating tumor cells (CTCs) allowed us to establish 5 CTC cell lines (BHGc7, 10, 16, 26 and UHGc5) from patients with recurrent SCLC. These cell lines exhibit the typical SCLC markers and CTCs of all patients developed spontaneously large multicellular aggregates, termed tumorospheres. Ki67 and carbonic anhydrase 9 (CAIX) staining of tumorosphere sections revealed quiescent and hypoxic cells, respectively. Accordingly, comparison of the chemosensitivity of CTC single cell suspensions with tumorospheres demonstrated increased resistance of the clusters against chemotherapeutics commonly used for treatment of SCLC. Therefore, global chemoresistance of relapsing SCLC seems to rely on formation of large tumorospheres which reveal limited accessibility, lower growth fraction and hypoxic conditions. Since similar tumor spheroids were found in other tumor types, SCLC seems to represent a unique tumor model to study the association of CTCs, metastasis and drug resistance.
format	article
author	Lukas Klameth Barbara Rath Maximilian Hochmaier Doris Moser Marlene Redl Felicitas Mungenast Katharina Gelles Ernst Ulsperger Robert Zeillinger Gerhard Hamilton
author_facet	Lukas Klameth Barbara Rath Maximilian Hochmaier Doris Moser Marlene Redl Felicitas Mungenast Katharina Gelles Ernst Ulsperger Robert Zeillinger Gerhard Hamilton
author_sort	Lukas Klameth
title	Small cell lung cancer: model of circulating tumor cell tumorospheres in chemoresistance
title_short	Small cell lung cancer: model of circulating tumor cell tumorospheres in chemoresistance
title_full	Small cell lung cancer: model of circulating tumor cell tumorospheres in chemoresistance
title_fullStr	Small cell lung cancer: model of circulating tumor cell tumorospheres in chemoresistance
title_full_unstemmed	Small cell lung cancer: model of circulating tumor cell tumorospheres in chemoresistance
title_sort	small cell lung cancer: model of circulating tumor cell tumorospheres in chemoresistance
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a2cf85fb0b7042ae8e2904ae222c0bb0
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Small cell lung cancer: model of circulating tumor cell tumorospheres in chemoresistance

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