CLDN6, or Claudin-6, is a protein of growing interest in biological research. Its unique expression patterns and connections to various biological processes offer insights into cell interactions and how they change in certain conditions.
Understanding CLDN6
CLDN6 is a member of the claudin protein family, integral to tight junctions. It has four segments that span the cell membrane, two extracellular loops, and one amino-terminal and one carboxy-terminal end inside the cell.
These structural features enable CLDN6 to participate in cell adhesion and signaling pathways. CLDN6 is found at cell-cell junctions, specifically within tight junctions that connect adjacent cells. Its gene is located on human chromosome 16.
How CLDN6 Works in Healthy Cells
In healthy tissues, CLDN6 forms tight junctions between cells. These junctions seal spaces between cells, creating a barrier that regulates the passage of molecules and ions. This function maintains tissue integrity and controls paracellular permeability, the movement of substances between cells.
CLDN6 contributes to the epidermal permeability barrier, the skin’s outermost layer that prevents water loss and protects against external substances. It also regulates the lung epithelial barrier. During embryonic development, CLDN6 is expressed in various epithelial tissues, including the stomach, pancreas, lung, and kidney, where it induces epithelial cell junction formation and polarity, and aids in stem cell differentiation.
CLDN6’s Role in Cancer
CLDN6 expression is altered in various cancers. While it is absent or expressed at very low levels in healthy adult tissues, its abnormal expression is observed in numerous tumor types. This pattern suggests a link to tumor development and progression.
In some cancers, such as ovarian, liver, endometrial, and esophageal cancers, CLDN6 is highly expressed in tumor tissues but not in surrounding normal tissues. For instance, in ovarian cancer, high CLDN6 expression promotes cell proliferation, migration, and invasion, while inhibiting apoptosis. Conversely, in breast cancers, CLDN6 overexpression can inhibit proliferation and promote apoptosis, suggesting a tumor-suppressive role. In hepatocellular carcinoma, CLDN6 can promote epithelial-mesenchymal transition (EMT) and enhance the proliferation and invasion of hepatoma cells. The varying roles of CLDN6 across different tumor types underscore the need for cancer-specific approaches.
Targeting CLDN6 for Treatment
CLDN6’s distinct expression in many cancers, with low or absent presence in healthy adult tissues, makes it a target for therapeutic development. Researchers are exploring approaches that leverage this specificity to selectively target cancer cells while minimizing harm to healthy cells.
One strategy involves antibody-drug conjugates (ADCs), which deliver potent chemotherapy directly to CLDN6-expressing cancer cells. ADCs bind to CLDN6 on the tumor cell surface, are internalized, and release the therapeutic agent inside the cancer cell. Another approach is CAR T-cell therapy, where a patient’s immune cells are genetically engineered to recognize and attack CLDN6-expressing tumor cells. Early clinical trials, such as a phase 1 study with BNT211, a CLDN6-targeting CAR T-cell product, have shown results in patients with CLDN6-positive advanced solid tumors like testicular and ovarian cancer. These therapies aim to eliminate cancer cells, offering new treatment options.