[A] 1.74 The tumor-organism relationship (tumor progression, heterogeneity, metabolism of tumor cells, cancer anorexia-cachexia syndrome, paraneoplasia, tumor immunity) Flashcards
Tumour progression
“Increase of the tumour’s malignant potential”
- Neoplastic transformation (neoplastic stem cell)
- Invasion ability
- Metastasis
- Generalisation
Tumour heterogeneity: Hypothesis
- The mutation of 1 cell is in the background
- The tumour is monoclonal
Tumour heterogeneity
- Genetic damage in tissue stem cells → Immortalise
- Monoclonal tumour cells mutate further → Genetic heterogeneity
Can lead to tumour subclones
Define: Heterogeneity
Being diverse in quality or character
Tumour heterogeneity: Positive selection with…
- Less antigenic tumour
- Fast-growing
- Ability to metastasise
- Low need of GF
- Resistance against cytostatic agents
Tumour heterogeneity: Result
Dominant, resistant tumour subpopulations
Relationship between tumour and the host?
- Competitive, disharmonic relationship with the host
- Autonomous growth
- Loss of BW; asthenia; immunosuppression; recurring infections; metabolic crisis
Metabolism of tumour cells
- Constant glucose supply in the body
- Genetic instability
- Adhesion and proliferation in hypoxic environment
- Non-oxidative processes
- Decreased FA and Aa synthesis
- Increased proliferation rate:
- Undifferentiated, low functioning cells
Metabolism of tumour cells: Genetic instability
- Increased proliferation rate
- Change of metabolism
- Increased need of RNA & DNA
Metabolism of tumour cells: Non-oxidative processes
Activated intracellularly
Cancer anorexia-cachexia syndrome
- Frequent in case of carcinomas
- Multifactorial
- Cachectic mediators
- Tumour-derived factors
- Host’s humoral factors
Cancer anorexia-cachexia syndrome: Clinical turnout
- Anorexia
- Early satiety
- Emaciation
- Anaemia
- Asthenia, weakness
Cancer cachexia
- Host’s macrophages/lymphocytes → Activated → Cytokines
- TNF and IL-1 induce leptin expression
- Hypothalamus → CRF
- CRF is norexigenic → Animal will feel full
Cancer cachexia: Processes that follow
- Tumour cells → Proteolysis-inducing factor (PIF)
- Increased metabolism in muscle & adipose
Muscle atrophy; Hormonal changes; Glucose intolerance; Insulin resistance
Paraneoplasia
Often follows neoplasia
- Humoral symptoms
- Biologically active compounds produced by bacteria
Paraneoplastic changes
- Tumour cachexia
- Hormonal symptoms
- Paraneoplastic skin lesions
- Hematologic symptoms
- Hemostatic changes (thrombophilia, DIC)
- Musculoskeletal symptoms
- Amyloidosis
- Pyrexia
- Nephropathies
Paraneoplastic changes: Hormonal symptoms
Ectopic hormone production
- Not normal in tissue of origin
- E.g Dog: Mediastinal lymphoma → Parathormone-like peptide → Hypercalcalcaemia
Paraneoplastic changes: Feminisation syndrome
In case of oestrogen-producing testicular tumours
- Bilateral symmetric alopecia
- Gynecomastia
- Myelosuppression
- Changes in behaviour
Anti-tumour effector cells
- Cytotoxic T-cell → Antigen recognition
- NK cells → Direct lysis
- Macrophages - TNFα, ROS
- Increase apoptosis
- Inhibition of angiogenesis
- Humoral processes - Complement system activation
Tumour specific antigens (TSA)
- Only on tumour cells
- Increased expression in case of E.g seminoma/melanoma
- Increased lymphocytic infiltration means usually a better prognosis
Tumour immunity: Causes
- Anti-tumour effector cells
- Tumour specific antigens (TSA)
- Tumour-associated antigens (TAA)
- Microevolutionary causes
Tumour-associated antigens (TAA)
- Next to tumour cells
- Some normal cells can also express these
Tumour immunity: Race between neoplasia and the immune system
- The selective proliferation of non-antigenic tumour cells
- Modulation or losing of tumour antigens
- Antigens binding to normal cells nearby (False target)
- Antigen covering by the fibrin network
- Losing of proteins aiding tumour recognition
- Lymphocytes can increase angiogenesis
- Immunosuppression
