Invasiveness and Chemoresistance of Cancer Stem Cells in Colon Cancer

Invasiveness and Chemoresistance of Cancer Stem Cells in Colon Cancer: Molecular Characterization and Implications for Therapeutic Strategies

The main objective of this study is to identify and characterize subpopulations of cells with invasive capacity in colorectal cancer from primary tumor, blood and metastatic samples.

Study Overview

• Status: Completed
• Conditions: Colorectal Neoplasms
• Intervention / Treatment: Biological: Samples and follow up

Detailed Description

Secondary objectives include:

• Determine the intrinsic properties essential for the dissemination and chemoresistance of these cells capable of initiating tumors
• Identify a "molecular signature" for potential invasiveness and chemoresistance of cells initiating metastases.
• Describe the evolution of patients during 24 months of follow up and correlations with observed cellular profiles.
• Enrich the tumor bank of the institution.

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• France
  • Gard
    • Nîmes Cedex 09, Gard, France, 30029
      • CHU de Nimes - Hopital Universitaire Caremeau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with operable, stage III or IV, adenocarcino-type colorectal cancer treated at the Nîmes University Hospital.

Description

Inclusion Criteria:

• The patient must have given his/her informed and signed consent
• The patient must be insured or beneficiary of a health insurance plan
• Patient with adenocarcinoma-type colorectal cancer:
• stage III at diagnosis, surgical resection of the primary tumor proposed.
• stage IV at diagnosis, surgical resection of the primary tumor and possibly of metastases proposed.
• Stage IV who have already undergone surgical excision of the primary tumor, and for whom metastasectomy is now proposed.

Exclusion Criteria:

• The patient is participating in another study
• The patient is in an exclusion period determined by a previous study
• The patient is under judicial protection, under tutorship or curatorship
• The patient refuses to sign the consent
• It is impossible to correctly inform the patient
• Patients for whom surgical resection of the primary tumor is not considered as an option
• PStage IV at diagnosis, but metastasectomy is not considered as an option
• Patients with positive HIV, Hepatitis B or Hepatitis C serology

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
30 Patients; Patients with operable, stage III or IV, adenocarcino-type colorectal cancer treated at the Nîmes University Hospital. Intervention: Samples and follow up	Biological: Samples and follow up; Samples: Peroperative blood sample plus primary and metastatic tumor biopsies. Follow-up: disease outcomes assessed at 24 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ability to maintain the cells isolated from colorectal tumors in culture or 3D collagen matrices and then infect these cells to make them express reporter genes: yes/no.	Baseline (Day 0)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serology HIV		baseline; day 0
Serology Hepatitis B		baseline; day 0
Serology Hepatitis C		baseline; day 0
Location of primary tumor	right colon, left colon, transverse colon, sigmoid, rectum	base line; day 0
Age at diagnosis		baseline, day 0
Metastases from the outset: Yes / No		baseline, day 0
Resection proposed: yes/no		baseline, day 0
Chemotherapy proposed? yes/no		baseline, day 0
Number of metastases		24 months
Resection performed: yes/no		24 months
Number of chemotherapy sessions performed		24 months
Objective tumoral response to treatment? yes/no		24 months
Tumor recurrence: yes/no		24 months
Vital status	living/deceased	24 months
Ability to establish tumor xenografts from injected cells: yes/no.		baseline; Day 0
Ability to detect subpopulations of tumor cells expressing fluorophores by flow cytometry after isolation: yes/no		baseline; day 0
Characterization of mRNA expression profiling and micro-RNA + in vitro EMT cells		baseline; day 0
World Health Organisation Score		24 months
Tumor staging		24 months
Number of surgeries performed		24 months
Number of circulating cancer cells per ml blood		baseline; day 0

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Jean-François Bourgaux, MD, Centre Hospitalier Universitaire de Nîmes

Publications and helpful links

General Publications

• Grillet F, Bayet E, Villeronce O, Zappia L, Lagerqvist EL, Lunke S, Charafe-Jauffret E, Pham K, Molck C, Rolland N, Bourgaux JF, Prudhomme M, Philippe C, Bravo S, Boyer JC, Canterel-Thouennon L, Taylor GR, Hsu A, Pascussi JM, Hollande F, Pannequin J. Circulating tumour cells from patients with colorectal cancer have cancer stem cell hallmarks in ex vivo culture. Gut. 2017 Oct;66(10):1802-1810. doi: 10.1136/gutjnl-2016-311447. Epub 2016 Jul 25.

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2012
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: April 12, 2012
• First Submitted That Met QC Criteria: April 13, 2012
• First Posted (Estimate): April 16, 2012

Study Record Updates

• Last Update Posted (Actual): June 21, 2021
• Last Update Submitted That Met QC Criteria: June 18, 2021
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: invasive potential; molecular characterisation of circulating cells
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: LOCAL/2011/JFB-01; 2011-A01141-40 (Other Identifier: RCB number)