As far as diseases go, few are met with more interest and concern than cancer. Cancers are the second leading cause of death in the U.S. and the subject of an immense body of research. Treatments for cancer are notoriously hard on the body and in many cases can only delay the progression of the disease.
But what makes cancer so difficult to treat? Cancer is caused by rogue cells in the body that lose the ability to regulate their growth and reproduction. Rather than serving their biological function, these cells will rapidly and uncontrollably reproduce, consuming valuable space and resources. This type of illness is very difficult for the body to recognize and fight, as the harmful agent is composed of the body’s own cells.
For the same reasons, clinical treatments for cancer are also very difficult to develop. Procedures or medications that will harm the cancer cells are also generally harmful to the rest of the patient. A very delicate balance must be kept between eliminating the cancer and minimizing harm to the patient. Most successful treatments rely on exploiting the subtle differences between cancerous and healthy cells to preferentially eliminate the disease. By studying the ways cancer cells deviate from their healthy counterparts, scientists can help develop new ways to treat cancer while minimizing damage to the rest of the body.
One process that is of particular interest to researchers is metastasis. Metastasis refers to the spreading of cancerous cells outside of a localized tumor, resulting in cancerous growth throughout the body. This presents an enormous challenge for treatment, as doctors cannot simply remove the cancerous region. Metastasized cancer is associated with significantly higher mortality, resistance to treatment, and increased recurrence of cancer after treatment.
Researchers at Kings College in London have recently uncovered a mechanism through which skin cancer cells can migrate through tissue and out of a tumor. When moving through these regions, a cell must navigate through a network of cells and other components, often encountering constrictions smaller than the cell itself. While the outer membrane of the cell is usually flexible enough to fit through these constrictions, this ability is often limited by less flexible components in the cell, in particular the nucleus. The nucleus serves as storage for the cell’s genetic material and is vital to its ability to grow and reproduce. When the nucleus is subjected to large mechanical stresses during cell migration, it can burst, resulting in cell death.
However, in cases of metastatic melanoma, this limit is overcome, allowing cells to squeeze through dense tissue and invade other parts of the body. To further examine this mechanism, researchers constructed a system of increasingly small pores through which different cancer cells were allowed to migrate. By closely analyzing the cells before and after migration, they were able to determine how factors like cell death or structural change were affected by constrictions. Understanding these relationships is a key step toward understanding the specific differences between cancerous cells and healthy ones.
Through their experiments, the team found that a specific protein called LAP1 was strongly associated with increased cell survival after constriction. Cells with higher expression of that protein were able to adapt the shape of their nucleus to migrate through tight junctions. In addition to the laboratory experiments, the team also investigated melanoma cells taken from a set of patients. They found that the LAP1 protein was expressed at much higher levels in patients where metastatic spread was found. This confirmed their finding that this protein plays a key role in the ability of cells to migrate in the body.
These findings present a valuable new perspective on the cellular mechanics of melanoma. Through identifying specific molecules or interactions that differentiate cancerous cells from healthy cells, scientists hope to improve our ability to design more specific diagnostic and treatment capabilities. When it comes to curing cancer, the role of translational, exploratory research plays an increasingly important role.
Image courtesy of Wikimedia Commons
