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PH-SD14

Tumour growth: kinetics, angiogenesis and heterogeneity

Why a tumour grows: cell production outpacing cell loss, the long silent period before it can be felt, the vessels it must recruit beyond a millimetre or two, and the competing clones that make every tumour a mosaic.

By the end, you can

  • Explain tumour growth as the balance of growth fraction, cell cycle time and cell loss, and why growth slows as a tumour enlarges.
  • Estimate how many cell doublings precede a clinically detectable tumour, and explain why that matters.
  • Describe the angiogenic switch, from hypoxia to VEGF to new, abnormal vessels.
  • Explain how genetic instability and selection produce clonal heterogeneity, and relate it to biopsy results and relapse.
  • Relate the zones of a growing tumour (perfused rim, hypoxic zone, necrotic core) to what imaging and pathology show.

What it is

Tumour growth biology describes how a neoplasm enlarges and changes over time: its kinetics (how many cells divide, how fast, and how many are lost), angiogenesis (the new blood vessels it induces once it outgrows diffusion), and heterogeneity (the genetic and non-genetic differences between its cells, which arise by clonal evolution and change under selection).

3 types to tell apart
Growth kinetics
Net growth is cell production minus cell loss. Production depends on the growth fraction and the cell cycle time; loss on apoptosis, necrosis and shedding.
Angiogenesis
New vessels sprout from existing ones when pro-angiogenic signals, chiefly VEGF, outweigh inhibitors. Tumour vessels are leaky and disorganised.
Heterogeneity
Differences between cells of one tumour (spatial and over time) and between tumours of the same type in different people.

US spelling: tumour → tumor.

Normal function

Normal tissues balance production and loss

Healthy tissues keep their size because cell production matches cell loss. In the small intestine, stem cells in the divide, their daughters divide a few more times as they climb, then stop dividing, mature and are shed from the tips of the within days. Most cells in the body are not dividing at all: they rest in G0, outside the cell cycle, until a signal recruits them.

Growth is restrained by checkpoints in the cell cycle (governed by proteins such as RB and p53), by contact with neighbours and by the supply of growth factors. Cells that are damaged or no longer needed are removed by apoptosis.

Every living cell must also be close to a capillary: oxygen diffuses only about 100 to 200 micrometres through tissue. When a tissue grows normally, as in wound healing or the endometrium each cycle, new vessels grow with it and stop when the need has passed.

Point to it on the model