Characteristics of Cancer Cells Notes

CHARACTERISTICS OF CANCER CELL

  • This presentation is for 1st-year students of JFMED CU in Martin and is for internal use only.

  • Copying is prohibited.

Cell Stability in Multicellular Organisms
  • The number of cells is relatively stable in multicellular organisms.

  • This stability is protected by:

  1. Regulation of cell proliferation.

  2. Regulation of cell death through apoptosis (programmed cell death).

  • During life, cells that can't respond to regulatory mechanisms can arise, proliferate without regulation, and form the basis for tumor development.

  • These changes are termed tumorous transformation of the cell.

  • A transformed cell behaves as a reproduction automaton, and its reproduction can't be influenced by signals from the cell's environment.

Characteristics of Cancer Cells
  1. Alterations in growth

  2. Cell surface alterations

  3. Cytoskeletal rearrangement

  4. Releasing of transforming growth factors

  5. Protease secretion

  6. Altered gene transcription

  7. Immortalization of cancer cell

Alterations in Growth
  • A key characteristic of transformed cells is that they continue to divide when normal cells stop dividing.

  • Decreased growth factor requirements:

    • Transformed cells have lost some of the hormone and growth factor requirements.

    • Transformed cells express both growth factors and their receptors – autocrine stimulation.

  • Loss of capacity of growth arrest:

    • Transformed cells continue dividing in decreased concentrations of nutrients.

    • Tumor cells may even kill themselves trying to continue growth in an insufficient environment.

Loss of Anchorage Dependence
  • Normal adherent cells require firm contact with the substratum for growth.

  • Most transformed cell lines have lost the requirement for adherence; they grow without attachment to a substratum.

Changes in Cell Morphology and Growth Habits
  • Transformed cells are very different in shape.

  • Transformed cells adhere poorly to each other;

  • Transformed cells form chaotic masses.

  • Loss of contact inhibition and movement:

    • When a normal cell is surrounded by others in such a way that it has nowhere to go, it stops movement - contact inhibition.

    • Transformed cells lack contact inhibition.

    • E-cadherin is a key component of the adherens.

Cell Surface Alterations
  • Increased mobility of surface proteins

    • The rearrangement of cytoskeletal elements has been considered a possible cause of the increased mobility of cell-surface proteins.

  • Changes in Fibronectin

    • Normal quiescent cells in monolayer culture become covered with a dense fibrillar network containing fibronectin as a major protein component.

    • Cancerous FN plays a tumor-suppressive role, whereas it is pro-metastatic and associated with poor prognosis.

Increased Glucose Transport
  • Transformed cells exhibit a high rate of glucose consumption beyond that necessary for ATP synthesis.

  • Glucose aids in the generation of biomass and regulates cellular signaling critical for oncogenic progression.

  • Glucose is uptaken by GLUT1, which is a glucose transporter overexpressed in cancer cells, and follows the glycolytic pathway to pyruvate.

Cytoskeletal Rearrangement
  • Under normal physiological conditions, the cytoskeletal network in the cell is resistant to deformation.

  • In malignant cells, reorganization of the cytoskeleton can occur.

  • Modifications in the arrangement of microtubules and microtubule-associated proteins (MAPs), microfilaments, and actin stress fibers.

    • Tubulin and MAPs - disease progression and chemoresistance.

    • Actin filaments disorganization - tumor formation, survival, metastasis.

    • Intermediate filaments reorganization - cell migration and invasion.

Transforming Growth Factors (TGFs)
  • Transforming growth factors α and β (TGFs) are proteins secreted by transformed cells.

  • TGF β:

    • Cancer cell proliferation

    • Suppression of immune response

    • Overproduction of extracellular matrix

  • TGF α:

    • Contributes to tumor-induced angiogenesis

Protease Secretion
  • Plasminogen activator may help the cells to penetrate the basal lamina - invasion by tumor cells – formation of metastases.

  • Transformed cells often secrete a protease called plasminogen activator, which cleaves a peptide bond in the serum protein plasminogen, converting it to the protease plasmin.

  • Normal cells treated