JAPAN — Researchers at Hokkaido University in Japan have developed a novel double-network (DN) hydrogel that effectively transformed cancer cells back into cancer stem cells (CSCs) within a mere 24 hours, across six different types of human cancer.

The findings of their study were published in Nature Biomedical Engineering.

The implications of this achievement are far-reaching, potentially leading to the development of new drugs that specifically target CSCs and the advancement of personalized medicines.

Despite advancements in cancer treatments, the survival rates for patients with advanced-stage cancer remain distressingly low.

One contributing factor is the presence of CSCs within cancer tissues, as these cells exhibit resistance to traditional chemotherapy and radiotherapy. CSCs can either lie dormant within the body or circulate, leading to cancer recurrence.

Professor Shinya Tanaka, one of the lead researchers, explains, “Cancer stem cells are a major target for anticancer drugs, but they are difficult to identify because they are present in very small numbers in cancer tissues. Understanding the molecular mechanisms of these stem cells is crucial for developing better cancer treatments.”

Current cancer therapies focus on removing tumors or destroying cancer cells. However, the persistence of CSCs, capable of self-reproduction and initiating tumor progression, poses a significant challenge, resulting in cancer recurrence and resistance to treatment.

Identifying and targeting CSCs with anti-cancer drugs could significantly enhance the effectiveness of cancer treatments.

CSCs are typically present in tumors in minute quantities, making their identification a daunting task. However, the use of hydrogels to create an artificial tumor environment has demonstrated the ability to increase the proportion of CSCs within tumors.

DN gels consist of two interlinked networks of polymers with distinct mechanical properties.

In this study, the DN gel incorporates a rigid strong polyelectrolyte gel as the first network and a flexible neutral polymer gel as the second network, resulting in a material with exceptional mechanical strength and toughness.

This DN gel acts as an artificial microenvironment that triggers cellular responses in CSCs. Principal investigator Shinya Tanaka describes the gel as a “potential weapon to fight cancer, with unique applications in regenerative medicine.”

The hydrogel possesses an elasticity that mimics the specific microenvironment required for CSCs, which can enhance stem cell-like behavior (stemness).

This, in turn, could facilitate more accurate detection of CSCs, improve cancer cell type diagnosis, and ultimately contribute to the production of personalized medicines.

To evaluate the effect of DN gels on cancer cells, the research team cultured six different human cancer cell lines on the hydrogel, including sarcoma, uterine cancer, lung cancer, colon cancer, bladder cancer, and brain cancer.

The sphere-like structures observed on the DN gel contained a significant proportion of CSCs, which are typically rare in primary tumors.

This suggests that the hydrogel interacts with differentiated cancer cells, reprogramming them into CSCs.

The researchers also examined glioblastoma, a malignant brain cancer with a disheartening five-year survival rate of only around 8%.

The DN gels induced CSCs rapidly in four patient-derived primary brain cancer cell lines. They observed a high expression of a protein called Sox2, responsible for cancer cell reprogramming, in the nuclei of sphere-forming cells.

This discovery sheds light on the molecular mechanisms underlying the hydrogel’s induction of stemness in cancer cells.

Furthermore, human brain cancer cells cultured on DN gels efficiently formed tumors when transplanted into mice.

The research team is currently focused on investigating how the inherent properties of DN gels impact cancer cells.

Specifically, they aim to understand how the chemical characteristics of the hydrogel influence the resulting stemness.

The development of this hydrogel marks a significant milestone in the field of cancer research, offering a promising avenue for combatting cancer by targeting CSCs.

As further investigations continue, the potential for personalized medicines tailored to individual patients becomes increasingly tangible, bringing hope to the battle against cancer.

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