Mitosis is the fundamental process by which a single parent cell divides to produce two genetically identical daughter cells. This mechanism underlies all tissue growth, repair, and replacement throughout an organism’s life. The entire cycle of cell growth and division is subject to a complex, internal control system known as the cell cycle. When this highly regulated system breaks down, the result is the loss of control over cellular reproduction.
The Failure of Cell Cycle Checkpoints
The strict progression through the cell cycle is governed by a series of internal monitoring points called checkpoints. These checkpoints assess the cell’s internal and external conditions before allowing the cell to advance to the next phase of division. Two families of proteins, cyclins and cyclin-dependent kinases (CDKs), are responsible for driving the cell forward. Cyclins are synthesized and degraded in a cyclical pattern, and they must bind to CDKs to activate the enzymatic activity necessary for cell division.
Mutations in the genes that encode these regulatory proteins can dismantle the control system. For example, the G1 checkpoint guards against the replication of damaged DNA and relies on molecules that halt the cycle until repairs are complete. Genes that normally suppress uncontrolled growth, known as tumor suppressor genes, function at these checkpoints to initiate repair or programmed cell death if damage is irreparable. One well-known protein detects DNA damage and attempts to correct it before the cell divides.
If a tumor suppressor gene becomes inactivated through mutation, its braking function is lost, allowing a genetically unstable cell to proceed with division. Conversely, other genes, called proto-oncogenes, promote cell growth and division under normal circumstances. When these proto-oncogenes acquire gain-of-function mutations, they become oncogenes, acting like a continuously pressed accelerator pedal for the cell cycle. The combined effect of losing the cellular brakes and permanently engaging the accelerator leads to uncontrolled cell division.
The Formation of Neoplasms
The immediate consequence of unchecked mitosis is the formation of an abnormal mass of cells, termed a neoplasm, meaning “new growth.” This excessive proliferation occurs because the cells ignore the normal signals that would stop their division. A distinguishing feature of these cells is the loss of contact inhibition, a property that causes normal cells to stop dividing when they physically touch one another.
A key distinction exists between the types of neoplasms. Benign neoplasms are slow-growing, remain localized to their site of origin, and are surrounded by a distinct fibrous capsule. These masses do not invade the surrounding normal tissue, and the cells often retain a relatively normal, differentiated appearance. They may still cause problems due to their size or location, but they do not pose the systemic threat of a malignant growth.
Malignant neoplasms exhibit a more aggressive and destructive pattern of growth. These cells are often poorly differentiated, meaning they look less like the healthy cells of the tissue they originated from. They lack the containment of a capsule and actively invade and destroy the neighboring tissue structures. Furthermore, many of these abnormal cells acquire the ability to divide indefinitely, bypassing the natural limits on replication.
Progression to Malignancy and Metastasis
The most dangerous outcome of uncontrolled mitosis is metastasis, the systemic spread of malignant cells. This process transforms a localized disease into one that affects distant organs and is responsible for the majority of related deaths. The metastatic cascade begins when cells from the primary malignant mass detach from their neighbors and break through the surrounding basement membrane and extracellular matrix.
Once freed, these cells invade the walls of nearby blood or lymphatic vessels, a process termed intravasation. Surviving in the circulation is challenging, as most circulating cells succumb to the immune system or the physical stress of the blood flow. Those that survive exit the vessel system at a distant site through a mechanism called extravasation.
The final stage of metastasis is the colonization of the new distant tissue. The malignant cells must adapt to the foreign microenvironment and begin to proliferate, forming a secondary, or metastatic, tumor. The establishment of these new colonies defines the advanced stage of the disease. This systemic spread is inefficient, yet the few cells that successfully complete the cascade are sufficient to establish life-threatening secondary growths.