Pancreatic cancer tumorspheres are cancer stem-like cells with increased chemoresistance and reduced metabolic potential
Cancer stem cells are a population of slow-cycling cells within the tumour bulk, with self-renewal capacity that attracts interest as a therapeutic target. In highly heterogeneous tumours, like pancreatic ductal adenocarcinoma (PDAC) however, the characterisation of cancer stem cells has led to cont...
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| Veröffentlicht in: | Advances in biological regulation 2019-05, Vol.72, p.63-77 |
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| creator | Domenichini, Alice Edmands, Jeanne S. Adamska, Aleksandra Begicevic, Romana-Rea Paternoster, Silvano Falasca, Marco |
| description | Cancer stem cells are a population of slow-cycling cells within the tumour bulk, with self-renewal capacity that attracts interest as a therapeutic target. In highly heterogeneous tumours, like pancreatic ductal adenocarcinoma (PDAC) however, the characterisation of cancer stem cells has led to controversial results due to the lack of consensus on specific markers. Here we investigated the characteristics of a population of pancreatic cancer tumorspheres derived from different human pancreatic cancer cell lines and a primary line from a genetically engineered KPC mouse model, using flow cytometry and western blotting to analyse surface and stemness markers. We analysed tumorspheres tumorigenic potential using anchorage-independent soft agar assay as well as their metabolic plasticity and chemoresistance. Pancreatic cancer tumorspheres display a heterogeneous pattern of surface and stemness markers, nevertheless they are characterised by an increased tumorigenic potential and higher chemoresistance. In addition, we have shown that pancreatic cancer tumorspheres have a unique metabolic profile with reduced metabolic potential. Together our results indicate that, despite the heterogeneity characterising pancreatic cancer tumorspheres, we can identify a functional vulnerability that represents a window for pharmacological intervention and development of novel therapeutic strategies.
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| doi_str_mv | 10.1016/j.jbior.2019.02.001 |
| format | Article |
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[Display omitted]</description><subject>Adenocarcinoma</subject><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biomarkers</subject><subject>Cancer</subject><subject>Cancer spheroids</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cell self-renewal</subject><subject>Chemoresistance</subject><subject>Drug Resistance, Neoplasm</subject><subject>Flow cytometry</subject><subject>Genetic engineering</subject><subject>Heterogeneity</subject><subject>Humans</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Neoplastic Stem Cells - cytology</subject><subject>Neoplastic Stem Cells - drug effects</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - drug therapy</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - physiopathology</subject><subject>Pharmacology</subject><subject>Spheroids, Cellular - cytology</subject><subject>Spheroids, Cellular - drug effects</subject><subject>Spheroids, Cellular - metabolism</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Therapeutic applications</subject><subject>Tumor cell lines</subject><subject>Tumorigenic potential</subject><subject>Tumors</subject><subject>Tumour initiating cells</subject><subject>Western blotting</subject><issn>2212-4926</issn><issn>2212-4934</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1P3DAQhq2qqKCFX4BUReqFS1J_ZJ34wKFalQ8JqRzgbPljonWaxIvtUPj3eHdhDxzqi0fj553xzIvQOcEVwYT_7KteOx8qiomoMK0wJl_QCaWElrVg9ddDTPkxOouxx_nwrKyX39Axw-2SsZqeoJd7NZkAKjlTmBxCKNI8-hA3awgQCxXgIx8TjOXg_uYEDEMs_rm0LtxOHcEWZg1ZB9HFtOULNdkigJ1NfhshKe2H3GPjE0zJqeEUHXVqiHD2fi_Q49Xvh9VNeffn-nb16640DNNUCqGw0Ip11hhdm47yRi0t4RaYbfJ0WAMnjWaqtlrorsW15m1rl6wxrNMa2AJd7Otugn-aISY5urgdQE3g5ygpEZiQlnKS0R-f0N7PYcq_k5QyygUTdZMptqdM8DEG6OQmuFGFV0mw3Hoje7nzRm69kZjK7E1WfX-vPesR7EHz4UQGLvcA5GU8OwgyGgd5kdYFMEla7_7b4A2E0qMO</recordid><startdate>20190501</startdate><enddate>20190501</enddate><creator>Domenichini, Alice</creator><creator>Edmands, Jeanne S.</creator><creator>Adamska, Aleksandra</creator><creator>Begicevic, Romana-Rea</creator><creator>Paternoster, Silvano</creator><creator>Falasca, Marco</creator><general>Elsevier Ltd</general><general>Elsevier BV</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20190501</creationdate><title>Pancreatic cancer tumorspheres are cancer stem-like cells with increased chemoresistance and reduced metabolic potential</title><author>Domenichini, Alice ; Edmands, Jeanne S. ; Adamska, Aleksandra ; Begicevic, Romana-Rea ; Paternoster, Silvano ; Falasca, Marco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c302t-99a09ba3fdccb4cf267a5d16de3d74920be617b3a4db9bf804b688d537c3fbbe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adenocarcinoma</topic><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biomarkers</topic><topic>Cancer</topic><topic>Cancer spheroids</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cell self-renewal</topic><topic>Chemoresistance</topic><topic>Drug Resistance, Neoplasm</topic><topic>Flow cytometry</topic><topic>Genetic engineering</topic><topic>Heterogeneity</topic><topic>Humans</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Neoplastic Stem Cells - cytology</topic><topic>Neoplastic Stem Cells - drug effects</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - drug therapy</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - physiopathology</topic><topic>Pharmacology</topic><topic>Spheroids, Cellular - cytology</topic><topic>Spheroids, Cellular - drug effects</topic><topic>Spheroids, Cellular - metabolism</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Therapeutic applications</topic><topic>Tumor cell lines</topic><topic>Tumorigenic potential</topic><topic>Tumors</topic><topic>Tumour initiating cells</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Domenichini, Alice</creatorcontrib><creatorcontrib>Edmands, Jeanne S.</creatorcontrib><creatorcontrib>Adamska, Aleksandra</creatorcontrib><creatorcontrib>Begicevic, Romana-Rea</creatorcontrib><creatorcontrib>Paternoster, Silvano</creatorcontrib><creatorcontrib>Falasca, Marco</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Advances in biological regulation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Domenichini, Alice</au><au>Edmands, Jeanne S.</au><au>Adamska, Aleksandra</au><au>Begicevic, Romana-Rea</au><au>Paternoster, Silvano</au><au>Falasca, Marco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pancreatic cancer tumorspheres are cancer stem-like cells with increased chemoresistance and reduced metabolic potential</atitle><jtitle>Advances in biological regulation</jtitle><addtitle>Adv Biol Regul</addtitle><date>2019-05-01</date><risdate>2019</risdate><volume>72</volume><spage>63</spage><epage>77</epage><pages>63-77</pages><issn>2212-4926</issn><eissn>2212-4934</eissn><abstract>Cancer stem cells are a population of slow-cycling cells within the tumour bulk, with self-renewal capacity that attracts interest as a therapeutic target. In highly heterogeneous tumours, like pancreatic ductal adenocarcinoma (PDAC) however, the characterisation of cancer stem cells has led to controversial results due to the lack of consensus on specific markers. Here we investigated the characteristics of a population of pancreatic cancer tumorspheres derived from different human pancreatic cancer cell lines and a primary line from a genetically engineered KPC mouse model, using flow cytometry and western blotting to analyse surface and stemness markers. We analysed tumorspheres tumorigenic potential using anchorage-independent soft agar assay as well as their metabolic plasticity and chemoresistance. Pancreatic cancer tumorspheres display a heterogeneous pattern of surface and stemness markers, nevertheless they are characterised by an increased tumorigenic potential and higher chemoresistance. In addition, we have shown that pancreatic cancer tumorspheres have a unique metabolic profile with reduced metabolic potential. Together our results indicate that, despite the heterogeneity characterising pancreatic cancer tumorspheres, we can identify a functional vulnerability that represents a window for pharmacological intervention and development of novel therapeutic strategies.
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| subjects | Adenocarcinoma Animals Antineoplastic Agents - pharmacology Biomarkers Cancer Cancer spheroids Cell Line, Tumor Cell Proliferation Cell self-renewal Chemoresistance Drug Resistance, Neoplasm Flow cytometry Genetic engineering Heterogeneity Humans Metabolism Mice Neoplastic Stem Cells - cytology Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - metabolism Pancreatic cancer Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - physiopathology Pharmacology Spheroids, Cellular - cytology Spheroids, Cellular - drug effects Spheroids, Cellular - metabolism Stem cell transplantation Stem cells Therapeutic applications Tumor cell lines Tumorigenic potential Tumors Tumour initiating cells Western blotting |
| title | Pancreatic cancer tumorspheres are cancer stem-like cells with increased chemoresistance and reduced metabolic potential |
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