Cellular Changes Involved in Tumor Formation

Introduction:

• Tumor formation (or tumorigenesis) involves a series of genetic and cellular changes that transform normal cells into cancerous cells.
• These changes disrupt the normal regulation of cell growth, division, and death, leading to uncontrolled proliferation and tumor development.

 

Key Cellular Changes in Tumor Formation:

1. Genetic Mutations:
• Definition: Alterations in DNA sequence.
• Types:
• Oncogenes Activation: Mutated proto-oncogenes promote uncontrolled cell division (e.g., RAS gene).
• Tumor Suppressor Genes Inactivation: Loss of genes that control cell division (e.g., p53, RB).
• DNA Repair Deficiency: Impaired mechanisms lead to the accumulation of mutations (e.g., BRCA1/2 mutations).
2. Loss of Contact Inhibition:
• Normal cells stop dividing when they touch neighboring cells.
• Tumor cells lose this property, leading to uncontrolled growth and tumor mass formation.
3. Loss of Apoptosis (Programmed Cell Death):
• Apoptosis removes damaged or abnormal cells.
• Cancer cells evade apoptosis by overexpressing anti-apoptotic proteins (e.g., BCL-2) or inactivating pro-apoptotic signals.
4. Immortality (Telomerase Activation):
• Normal cells have a limited number of divisions due to telomere shortening.
• Cancer cells maintain telomere length by activating telomerase, enabling indefinite division.
5. Anchorage-Independent Growth:
• Normal cells need attachment to a surface for growth.
• Tumor cells can grow without attachment, enabling them to survive and proliferate in suspension or metastasize.
6. Angiogenesis (Formation of New Blood Vessels):
• Tumors stimulate the growth of blood vessels to supply oxygen and nutrients.
• This process is driven by factors like VEGF (Vascular Endothelial Growth Factor).
7. Metabolic Reprogramming:
• Tumor cells switch to aerobic glycolysis (Warburg effect) even in the presence of oxygen.
• Provides intermediates for biosynthesis to support rapid growth.
8. Evading Immune Detection:
• Cancer cells avoid immune system destruction by:
• Downregulating MHC (Major Histocompatibility Complex) molecules.
• Producing immunosuppressive cytokines. 

9. Invasion and Metastasis:

•      Invasion: Tumor cells break through the basement membrane and invade surrounding tissues.
•       Metastasis: Spread of cancer cells through the bloodstream or lymphatic system to form secondary tumors in distant organs.

10. Role of Developmental Genes (Homeotic Genes):

·        In tumorigenesis, some genes involved in developmental processes (e.g., HOX genes) may become dysregulated, leading to abnormal tissue growth patterns similar to embryonic development.

 

Conclusion:

• Tumor formation involves a series of cellular and genetic changes that disrupt normal cell regulation.
• These changes include genetic mutations, loss of apoptosis, angiogenesis, and immune evasion, contributing to the development and progression of cancer.
• Understanding these mechanisms is crucial for developing targeted therapies to prevent or treat cancer