4.3 The Biology of Cancer Study Notes

Characteristics of normal cell division:
1. Cells divide only when it is appropriate for their type and circumstances, tightly regulated by cell cycle checkpoints that monitor DNA integrity and growth conditions.
2. Cells maintain their specialized differentiated identity, crucial for tissue function.
3. New cells are generated to replace old or damaged cells in a controlled manner.
Cancer cells are initiated when they lose the ability to be controlled within the cell cycle, leading to unchecked proliferation.

The outer layer of skin (epidermis) is approximately 12 cells thick.
Cells in the basal layer (bottom row):
- Divide just fast enough to replenish shed cells.
- When a basal cell divides, it produces two cells:
- One remains in the basal layer and retains the capacity to divide.
- The other migrates out and loses the capacity to divide, undergoing differentiation.

Skin cancer begins when the balance between cell division and cell loss is disrupted, often due to genetic alterations.
In this case, basal cells divide too rapidly, causing both daughter cells to retain the capacity to divide and ignore growth-inhibiting signals.
This leads to a growing mass of tissue known as a tumor or neoplasm, characterized by uncontrolled cell growth and often a failure to undergo programmed cell death (apoptosis).
As the number of dividing cells increases, the normal organization of tissue becomes disrupted.

Definition: Masses of cells that are no longer under normal control of division, capable of sustained growth.
Example: Warts (benign tumors)

Stem Cells:
- Unspecialized cells that can divide without limit and differentiate into specialized cells under specific conditions.
Cell Differentiation:
- Process where a cell changes from one type to many different types, involving differences in morphological structure and physiological function. In cancer, cells can sometimes lose their differentiated state (dedifferentiation).
All organisms begin from a single cell.

How do identical cells develop into different types?
Cell differentiation involves the activation or inactivation of certain genes.
Factors leading to gene activation:
1. Interactions with nearby cells (cell-cell interactions), transmitting signals that guide differentiation.
2. The surrounding environment (extracellular matrix, ECM), which provides biochemical and structural cues.
ECM: Provides structural support and regulates cell differentiation. Composed of a network of proteins, sugars, and other molecules found outside of cells in tissues.

In healthy tissues:
- Cells interact well with each other and the ECM to maintain tissue integrity and function, responding to signals for growth and cessation.
Cancerous cells:
- Disrupted interactions leading to uncontrolled growth, as they often fail to respond to normal growth-inhibiting signals from their environment.
Illustrates loss of responsiveness to the ECM and neighboring cells, a key characteristic of tumors.

Cells communicate through various signaling pathways essential for coordinating differentiation, growth, and survival.
In cancer, these mechanisms can lead to lost ability to sense ECM and neighboring cells, promoting tumor development and invasive behavior.

Genetic Mutations:
- Tumor cells accumulate mutations disrupting normal signaling paths for ECM and cell-cell communication, leading to uncontrolled growth. Key mutations often occur in oncogenes (which promote cell growth) and tumor suppressor genes (which normally inhibit cell growth).
Altered Cell-ECM Interactions:
- Changes in the interaction between cells and the ECM can enhance uncontrolled division by providing persistent growth signals, altering cell adhesion, and facilitating cell migration.
Loss of Contact Inhibition:
- Normal contact inhibition causes cells to stop dividing when they touch neighboring cells, forming a single layer. Tumor cells often lose this inhibition, leading to them piling up and growing in multiple layers.
- Cadherins: Proteins involved in cell adhesion that, when mutated or lost, result in the absence of contact inhibition, contributing to cancer progression.

Local Invasion: Cancers can spread within the same area by extending into adjacent tissues and organs.
Metastasis:
- Cancer cells travel via blood or lymph to establish secondary colonies in distant tissues. This complex process involves intravasation (entering blood/lymph vessels), survival in circulation, extravasation (exiting vessels), and colonization in a new site.

Hyperplasia:
- Increase in the number of cells in a tissue, leading to tissue enlargement; often benign but can lead to cancer if regulatory controls are compromised.

Abnormal changes in size, shape, and organization of cells indicating potential precancerous changes that may progress to cancer.

In Situ Cancer:
- Cancerous cells that remain in their original location without spreading nearby. This is considered an early stage of cancer and is typically highly treatable.
Invasive Cancer:
- Cancer cells that have spread beyond their original site and invaded nearby tissues, signaling a more advanced progression that might spread to other body parts through local invasion and metastasis.

Utilization of nutrients without contributing to functional processes, leading to severe weight loss and wasting (cachexia).
Expansion of tumors causing pressure on other organs, distorting them, or interfering with blood, lymphatic, or nervous access, leading to organ dysfunction.
Invasion and weakening of bone structures, increasing fracture risk and causing pain.
Production of chemicals that disrupt bodily functions including anorexia, inflammation, coagulation, pain, and blood pressure irregularities (paraneoplastic syndromes).
Evasion of the immune system, allowing uncontrolled growth and spread.

Instructor's Contact:
- Siamak Shirani Bidabadi
- Horticulture and Crop Science (Ph.D.)
- Email: sbidabad@asu.edu
Thank You!