04 Jun 2010

The University of Hong Kong Li Ka Shing Faculty of Medicine has conducted a study on human colorectal cancer that identified for the first time a subset of cancer stem cells (CSCs) responsible for metastasis in human colorectal cancer. Metastasis is the spread of a cancer to distant organs, a stage that leads to ultimate death in most cancer patients. The novel finding of the role of a subset of CSCs in metastasis is an important breakthrough that contributes to better prognostic prediction and treatment of cancer patients in the future. The research is published in “Cell Stem Cell”, the top journal in stem cell research.

One of the key researchers, Dr Roberta Pang Wen-chi, Research Assistant Professor of the Department of Medicine, HKU says, “Identification and characterization of this subpopulation of cancer stem cells will enable us to evaluate for different molecular targeting drugs that can specifically target these cells. In the long term, it should facilitate the development of more useful, safe and specific drugs that can be used in combination with chemotherapy to completely eradicate the tumour.”

About colorectal cancer

Colorectal cancer is a common cancer worldwide and also one of the three most common cancers in Hong Kong, with rapidly rising incidence in recent years (over 4000 new cases per year). It is predicted that it will become the most common cancer in Hong Kong in the next few years. Surgical and chemotherapy treatments of colorectal cancer are well-established, but it remains the second most common cause of cancer-related death worldwide, suggesting that current therapies are not adequate to cure the disease.

Conventional treatment for colorectal cancer and its deficiency:

Surgical resection is the mainstay of treatment, but even with adequate surgical removal of the primary tumour, distant metastasis develop in more than 50% of patients; and despite aggressive surgical resection or chemotherapy for the metastasis, most patients eventually succumb to the metastasis. Understanding the biological mechanism of metastasis is the key to improving patient survival for this common cancer.

HKU study on cancer stem cells in colorectal cancer

Recent evidence indicates that cancers contain a small population of CSCs that are responsible for tumour initiation and maintenance; they are more resistant to conventional treatments than the more mature cancer cells within the tumour, making it difficult to completely eradicate the cancer with current therapeutic regimens.

Researchers in HKU have successfully isolated a subpopulation of cancer cells endowed with stem cell properties that are responsible for initiating metastasis. Fresh specimens of primary colorectal cancer and liver metastatic tumours resected from patients were immediately processed to isolate CSCs using a panel of surface markers. CSCs, but not mature cancer cells, are capable of regenerating tumours with similar histology to the human cancers when injected into mice. The HKU researchers identified a specific marker, CD26, which marks a subset of CSCs with metastatic capacity. CD26+ CSCs are uniformly present in both the primary and metastatic tumours in colorectal cancer patients with liver metastasis. In other patients without distant metastasis at presentation, the presence of CD26+ CSCs in their primary tumours could predict the development of distant metastasis on follow-up. Isolated CD26+ CSCs, but not CD26- CSCs, from human colorectal cancer are capable of initiating distant metastasis when implanted into the colon of the mouse model.

Treatment of mice implanted with primary colorectal cancer using chemotherapy drugs currently used for the cancer led to initial tumour shrinkage but subsequent recurrence and liver metastasis, a phenomenon frequently seen in the clinical setting. Chemotherapy treatment enriches the subpopulation of CD26+ CSCs in the tumour, which is more chemo-resistant than other cancer cells within the tumour, explaining the failure of chemotherapeutic treatment frequently observed in the clinical setting.

The ability to predict metastasis based on the CD26+ CSCs in the primary tumour as a marker of metastasis may help selection of patients for adjuvant therapy. Furthermore, the identification of this subset of CSCs provides insight into a novel strategy to target these CSCs to more effectively prevent and treat metastasis in colorectal cancer.

Further studies

The HKU research team is conducting a further study to isolate the CD26+ CSCs in the blood of colorectal cancer patients, which will facilitate a much more convenient way of using circulating CD26+ CSCs as a predictive maker of metastasis even in patients with unresectable tumours. 　The team is also studying the specific molecular pathways responsible for the metastatic capacity of this subset of CSCs, with the aim of developing molecular targeted drugs to effectively inhibit metastasis in colorectal cancer.

About the HKU research team:

The ground-breaking research findings of this study are the results of collaboration between the Division of Gastroenterology and Hepatology of Department of Medicine (Professor Benjamin Wong Chun-yu and Dr Roberta Pang Wen-chi), Division of Colorectal Surgery (Professor Law Wai-lun) and Division of Hepatobiliary Surgery (Professor Ronnie Poon Tung-ping) of Department of Surgery, Li Ka Shing Faculty of Medicine, HKU, with contribution from the Centre for Cancer Research of HKU.

About Cell Stem Cell:

Cell Stem Cell is a monthly journal from Cell Press launched in June 2007, which is affiliated with the International Society for Stem Cell Research (ISSCR). It publishes research articles and review materials with a focus on stem cells. The journal was named “Best New Journal” of 2007 by the Professional and Scholarly Division of the Association of American Publishers, achieving an impact factor of 16.8 in 2 years since its launch; ranking first in stem cell research and top ten in medical sciences.

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