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Establishment and characterization of HROC69 - a Crohn´s related colonic carcinoma cell line and its matched patient-derived xenograft.

Kuehn F, Mullins CS, Krohn M, Harnack C, Ramer R, Krämer OH, Klar E, Huehns M, Linnebacher M - Sci Rep (2016)

Bottom Line: They show strong invasive but in comparison weak migratory activity.The present work is the first description of patient-derived in vitro and in vivo models for CAC from a Crohn´s disease patient.They might be valuable tools for analysis of genetic and epigenetic alterations, biomarker identification, functional testing, including response prediction, and the development of specific therapeutical strategies.

View Article: PubMed Central - PubMed

Affiliation: University Medicine Rostock, Department of General-, Thoracic-, Vascular- and Transplantation Surgery, Rostock, Germany.

ABSTRACT
Colitis-associated colorectal cancer (CAC) seems to be a rather unique entity and differs in its genetic alterations, tumour formation capacities, and clinical features from sporadic colorectal carcinoma. Most descriptions about tumour biology of CAC refer to ulcerative colitis; data about Crohn´s colitis related carcinomas are scarce. The majority of patients with Crohn´s disease are under immunosuppression which generates a different environment for tumour growth. We first describe the clinical case of a fast growing CAC in a long-term immunosuppressed patient with Crohn´s disease and successful establishment and characterization of carcinoma cell lines along with their corresponding patient-derived xenograft. Subsequently, these tumor models were molecularly and functionally analysed. Beside numerous chromosomal alterations, mutations in TP53, APC, PTEN and SMAD3 were identified. The cell lines express numerous cancer testis antigens, surface molecules involved in immune evasion but low levels of HLA class I molecules. They show strong invasive but in comparison weak migratory activity. The present work is the first description of patient-derived in vitro and in vivo models for CAC from a Crohn´s disease patient. They might be valuable tools for analysis of genetic and epigenetic alterations, biomarker identification, functional testing, including response prediction, and the development of specific therapeutical strategies.

No MeSH data available.


Related in: MedlinePlus

Patient tumour and model imaging.(A) CT-scan showing the large tumour affecting cecum and ascending colon (red surrounding)–without proof of distant metastases. (B) micro-photographs (20×) of the patient-derived cell line HROC69, an H&E stain of HROC69 PDX and an H&E stain of patient HROC69 tumour. The time for tumour (model) growth is indicated below each image.
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f1: Patient tumour and model imaging.(A) CT-scan showing the large tumour affecting cecum and ascending colon (red surrounding)–without proof of distant metastases. (B) micro-photographs (20×) of the patient-derived cell line HROC69, an H&E stain of HROC69 PDX and an H&E stain of patient HROC69 tumour. The time for tumour (model) growth is indicated below each image.

Mentions: We report on a 62 year old patient with longstanding CD of the colon and fistulising rectum manifestation. First diagnosis of CD was at patient’s age of 42 years. Because of complicated fistulising rectal disease, the patient was treated with a combination of azathioprine and the TNF-α-antibody infliximab for 9 years. Surgical consultations and interventions for abscess formation or fistula also took place. Azathioprine was applied daily according to body weight. Additionally, the patient received infliximab infusions every 8 weeks (52 infusions in total). In a surveillance colonoscopy a large carcinoma affecting cecum and ascending colon was detected. Crohn´s luminal activity was mild and mostly restricted to the rectum. One year before, the patient underwent surveillance pan-colonoscopy by the same physician showing rectal and perianal CD but no signs of malignant transformation. Luminal colonic disease was described as non-severe and mostly in remission. After completing diagnostics without proof of distal metastases (Fig. 1A), tumour resection was conducted by a right-sided hemicolectomy.


Establishment and characterization of HROC69 - a Crohn´s related colonic carcinoma cell line and its matched patient-derived xenograft.

Kuehn F, Mullins CS, Krohn M, Harnack C, Ramer R, Krämer OH, Klar E, Huehns M, Linnebacher M - Sci Rep (2016)

Patient tumour and model imaging.(A) CT-scan showing the large tumour affecting cecum and ascending colon (red surrounding)–without proof of distant metastases. (B) micro-photographs (20×) of the patient-derived cell line HROC69, an H&E stain of HROC69 PDX and an H&E stain of patient HROC69 tumour. The time for tumour (model) growth is indicated below each image.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834534&req=5

f1: Patient tumour and model imaging.(A) CT-scan showing the large tumour affecting cecum and ascending colon (red surrounding)–without proof of distant metastases. (B) micro-photographs (20×) of the patient-derived cell line HROC69, an H&E stain of HROC69 PDX and an H&E stain of patient HROC69 tumour. The time for tumour (model) growth is indicated below each image.
Mentions: We report on a 62 year old patient with longstanding CD of the colon and fistulising rectum manifestation. First diagnosis of CD was at patient’s age of 42 years. Because of complicated fistulising rectal disease, the patient was treated with a combination of azathioprine and the TNF-α-antibody infliximab for 9 years. Surgical consultations and interventions for abscess formation or fistula also took place. Azathioprine was applied daily according to body weight. Additionally, the patient received infliximab infusions every 8 weeks (52 infusions in total). In a surveillance colonoscopy a large carcinoma affecting cecum and ascending colon was detected. Crohn´s luminal activity was mild and mostly restricted to the rectum. One year before, the patient underwent surveillance pan-colonoscopy by the same physician showing rectal and perianal CD but no signs of malignant transformation. Luminal colonic disease was described as non-severe and mostly in remission. After completing diagnostics without proof of distal metastases (Fig. 1A), tumour resection was conducted by a right-sided hemicolectomy.

Bottom Line: They show strong invasive but in comparison weak migratory activity.The present work is the first description of patient-derived in vitro and in vivo models for CAC from a Crohn´s disease patient.They might be valuable tools for analysis of genetic and epigenetic alterations, biomarker identification, functional testing, including response prediction, and the development of specific therapeutical strategies.

View Article: PubMed Central - PubMed

Affiliation: University Medicine Rostock, Department of General-, Thoracic-, Vascular- and Transplantation Surgery, Rostock, Germany.

ABSTRACT
Colitis-associated colorectal cancer (CAC) seems to be a rather unique entity and differs in its genetic alterations, tumour formation capacities, and clinical features from sporadic colorectal carcinoma. Most descriptions about tumour biology of CAC refer to ulcerative colitis; data about Crohn´s colitis related carcinomas are scarce. The majority of patients with Crohn´s disease are under immunosuppression which generates a different environment for tumour growth. We first describe the clinical case of a fast growing CAC in a long-term immunosuppressed patient with Crohn´s disease and successful establishment and characterization of carcinoma cell lines along with their corresponding patient-derived xenograft. Subsequently, these tumor models were molecularly and functionally analysed. Beside numerous chromosomal alterations, mutations in TP53, APC, PTEN and SMAD3 were identified. The cell lines express numerous cancer testis antigens, surface molecules involved in immune evasion but low levels of HLA class I molecules. They show strong invasive but in comparison weak migratory activity. The present work is the first description of patient-derived in vitro and in vivo models for CAC from a Crohn´s disease patient. They might be valuable tools for analysis of genetic and epigenetic alterations, biomarker identification, functional testing, including response prediction, and the development of specific therapeutical strategies.

No MeSH data available.


Related in: MedlinePlus