Establishment, characterization and chemosensitivity of three mismatch repair deficient cell lines from sporadic and inherited colorectal carcinomas.
BACKGROUND: Colorectal cancer (CRC) represents a morphologic and molecular heterogenic disease. This heterogeneity substantially impairs drug effectiveness and prognosis. The subtype of mismatch repair deficient (MMR-D) CRCs, accounting for about 15% of all cases, shows particular differential respo...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3534085?pdf=render |
| _version_ | 1818897895762427904 |
|---|---|
| author | Claudia Maletzki Saskia Stier Ulrike Gruenert Michael Gock Christiane Ostwald Friedrich Prall Michael Linnebacher |
| author_facet | Claudia Maletzki Saskia Stier Ulrike Gruenert Michael Gock Christiane Ostwald Friedrich Prall Michael Linnebacher |
| author_sort | Claudia Maletzki |
| collection | DOAJ |
| description | BACKGROUND: Colorectal cancer (CRC) represents a morphologic and molecular heterogenic disease. This heterogeneity substantially impairs drug effectiveness and prognosis. The subtype of mismatch repair deficient (MMR-D) CRCs, accounting for about 15% of all cases, shows particular differential responses up to resistance towards currently approved cytostatic drugs. Pre-clinical in vitro models representing molecular features of MMR-D tumors are thus mandatory for identifying biomarkers that finally help to predict responses towards new cytostatic drugs. Here, we describe the successful establishment and characterization of three patient-derived MMR-D cell lines (HROC24, HROC87, and HROC113) along with their corresponding xenografts. METHODOLOGY: MMR-D cell lines (HROC24, HROC87, and HROC113) were established from a total of ten clinicopathological well-defined MMR-D cases (120 CRC cases in total). Cells were comprehensively characterized by phenotype, morphology, growth kinetics, invasiveness, and molecular profile. Additionally, response to clinically relevant chemotherapeutics was examined in vitro and in vivo. PRINCIPAL FINDINGS: Two MMR-D lines showing CIMP-H derived from sporadic CRC (HROC24: K-ras(wt), B-raf(mut), HROC87: K-ras(wt), B-raf(mut)), whereas the HROC113 cell line (K-ras(mut), B-raf(wt)) was HNPCC-associated. A diploid DNA-status could be verified by flow cytometry and SNP Array analysis. All cell lines were characterized as epithelial (EpCAM(+)) tumor cells, showing surface tumor marker expression (CEACAM(+)). MHC-class II was inducible by Interferon-γ stimulation. Growth kinetics as well as invasive potential was quite heterogeneous between individual lines. Besides, MMR-D cell lines exhibited distinct responsiveness towards chemotherapeutics, even when comparing in vitro and in vivo sensitivity. CONCLUSIONS: These newly established and well-characterized, low-passage MMR-D cell lines provide a useful tool for future investigations on the biological characteristics of MMR-D CRCs, both of sporadic and hereditary origin. Additionally, matched patient-derived immune cells allow for comparative genetic studies. |
| first_indexed | 2024-12-19T19:23:27Z |
| format | Article |
| id | doaj.art-87bf9c0afe7f430c85edff2b64705a38 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T19:23:27Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-87bf9c0afe7f430c85edff2b64705a382022-12-21T20:08:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5248510.1371/journal.pone.0052485Establishment, characterization and chemosensitivity of three mismatch repair deficient cell lines from sporadic and inherited colorectal carcinomas.Claudia MaletzkiSaskia StierUlrike GruenertMichael GockChristiane OstwaldFriedrich PrallMichael LinnebacherBACKGROUND: Colorectal cancer (CRC) represents a morphologic and molecular heterogenic disease. This heterogeneity substantially impairs drug effectiveness and prognosis. The subtype of mismatch repair deficient (MMR-D) CRCs, accounting for about 15% of all cases, shows particular differential responses up to resistance towards currently approved cytostatic drugs. Pre-clinical in vitro models representing molecular features of MMR-D tumors are thus mandatory for identifying biomarkers that finally help to predict responses towards new cytostatic drugs. Here, we describe the successful establishment and characterization of three patient-derived MMR-D cell lines (HROC24, HROC87, and HROC113) along with their corresponding xenografts. METHODOLOGY: MMR-D cell lines (HROC24, HROC87, and HROC113) were established from a total of ten clinicopathological well-defined MMR-D cases (120 CRC cases in total). Cells were comprehensively characterized by phenotype, morphology, growth kinetics, invasiveness, and molecular profile. Additionally, response to clinically relevant chemotherapeutics was examined in vitro and in vivo. PRINCIPAL FINDINGS: Two MMR-D lines showing CIMP-H derived from sporadic CRC (HROC24: K-ras(wt), B-raf(mut), HROC87: K-ras(wt), B-raf(mut)), whereas the HROC113 cell line (K-ras(mut), B-raf(wt)) was HNPCC-associated. A diploid DNA-status could be verified by flow cytometry and SNP Array analysis. All cell lines were characterized as epithelial (EpCAM(+)) tumor cells, showing surface tumor marker expression (CEACAM(+)). MHC-class II was inducible by Interferon-γ stimulation. Growth kinetics as well as invasive potential was quite heterogeneous between individual lines. Besides, MMR-D cell lines exhibited distinct responsiveness towards chemotherapeutics, even when comparing in vitro and in vivo sensitivity. CONCLUSIONS: These newly established and well-characterized, low-passage MMR-D cell lines provide a useful tool for future investigations on the biological characteristics of MMR-D CRCs, both of sporadic and hereditary origin. Additionally, matched patient-derived immune cells allow for comparative genetic studies.http://europepmc.org/articles/PMC3534085?pdf=render |
| spellingShingle | Claudia Maletzki Saskia Stier Ulrike Gruenert Michael Gock Christiane Ostwald Friedrich Prall Michael Linnebacher Establishment, characterization and chemosensitivity of three mismatch repair deficient cell lines from sporadic and inherited colorectal carcinomas. PLoS ONE |
| title | Establishment, characterization and chemosensitivity of three mismatch repair deficient cell lines from sporadic and inherited colorectal carcinomas. |
| title_full | Establishment, characterization and chemosensitivity of three mismatch repair deficient cell lines from sporadic and inherited colorectal carcinomas. |
| title_fullStr | Establishment, characterization and chemosensitivity of three mismatch repair deficient cell lines from sporadic and inherited colorectal carcinomas. |
| title_full_unstemmed | Establishment, characterization and chemosensitivity of three mismatch repair deficient cell lines from sporadic and inherited colorectal carcinomas. |
| title_short | Establishment, characterization and chemosensitivity of three mismatch repair deficient cell lines from sporadic and inherited colorectal carcinomas. |
| title_sort | establishment characterization and chemosensitivity of three mismatch repair deficient cell lines from sporadic and inherited colorectal carcinomas |
| url | http://europepmc.org/articles/PMC3534085?pdf=render |
| work_keys_str_mv | AT claudiamaletzki establishmentcharacterizationandchemosensitivityofthreemismatchrepairdeficientcelllinesfromsporadicandinheritedcolorectalcarcinomas AT saskiastier establishmentcharacterizationandchemosensitivityofthreemismatchrepairdeficientcelllinesfromsporadicandinheritedcolorectalcarcinomas AT ulrikegruenert establishmentcharacterizationandchemosensitivityofthreemismatchrepairdeficientcelllinesfromsporadicandinheritedcolorectalcarcinomas AT michaelgock establishmentcharacterizationandchemosensitivityofthreemismatchrepairdeficientcelllinesfromsporadicandinheritedcolorectalcarcinomas AT christianeostwald establishmentcharacterizationandchemosensitivityofthreemismatchrepairdeficientcelllinesfromsporadicandinheritedcolorectalcarcinomas AT friedrichprall establishmentcharacterizationandchemosensitivityofthreemismatchrepairdeficientcelllinesfromsporadicandinheritedcolorectalcarcinomas AT michaellinnebacher establishmentcharacterizationandchemosensitivityofthreemismatchrepairdeficientcelllinesfromsporadicandinheritedcolorectalcarcinomas |