In multicellular organisms the individual cells are subject to social control. Unlike free-living unicellular organisms, the members of a multicellular community must reduce or cease their multiplication at the right time and place. The process of terminal differentiation alone is associated with a delay in the cell cycle and thus causes a slowdown of cell multiplication. Frequently, terminal differentiation results in a complete cessation of growth. In mammals, for example, mature blood cells and nerve cells completely lose the ability to divide. Termination of growth in these cells is part of their normal developmental program. In contrast, stem cells and several types of progenitor cells must continue to divide.

Apoptosis, programmed cell death, terminates the life of individual cells in many cell types. Apoptosis was introduced in Chap. 14 (Fig. 14.​9) and will further be discussed in Chap. 21 (Ageing and Death) but must also be considered in theories on carcinogenesis.

Besides such endpoints programmed at the outset in the developmental progress cells remaining potentially immortal either self-regulate their proliferation rate or are controlled by their neighbours.

A simple model provides a plausible indication of how a population can automatically constrict its growth itself. Imagine all cells of a still small and loosely arranged cell society produce inhibitory substances, be it trivial metabolic end products or specific negative growth factors; the substances are released into the surrounding interstitial diffusion space having restricted capacity. Initially the density of the population would be low and so also the concentration of the inhibitory substance. With increasing cell number more and more producers are active but the diffusion space around each individual cell will not increase but shrink resulting in a steep slope upwards in concentration of the inhibitor. Eventually a threshold will be reached above which growth comes to a standstill. In addition, in large massive organs such as the liver, outflow of inhibitory substances decreases with enlargement of the organ since in relation to mass and cell number the surface area decreases.

In the scientific literature there is only rarely talk of signalling substances preventing growth probably because often clear distinctions cannot be made. Many growth factors stimulates proliferation of certain cells at low concentration but stop it at high concentration. In precursor cells capable of dividing (indicated by the suffix ‘-blasts’), for example in the blood forming hemangioblasts, myeloblasts and erythroblasts (Chap. 18) some of these factors promote proliferation at low concentration but induce terminal differentiation at high concentration. Hence such proteins are called differentiation factors or differentiation hormones. Moreover, in a given case it is difficult or even impossible to discriminate between specific and non-specific inhibition. Growth inhibiting signalling substances are not always soluble factors. On the contrary, in most tissues cell adhesion molecules CAM and components of the extracellular matrix provide such signals. This is indicated by the behaviour of dissociated cells which in cell culture resume dividing upon separation from the social society, and shown by the behaviour of cancer cells.

Cancer arises when basic rules of the cell-specific or social control of proliferation are violated. Excessive multiplication may occur in the following situations:

Transformation. The deterioration of a civilized cell into an antisocial cancer cell is called neoplastic transformation (Greek: neo = new; plastein = to form). Agents causing carcinogenesis are called carcinogenic (Latin/Greek: cancer-generating) or oncogenic (Greek: oncos = mass; genein = generating). However, the common use of the term ‘oncogene’ may be confusing. While the adjective oncogenic means “cancer generating”, the noun oncogene refers to a gene causing cancer.

A tumour (Latin = swelling) is an association of cancerous cells, generally deriving from one transformed founder cell. A tumour may be benign (Latin benignus = mild, good-natured) or malignant (Latin malignus = malicious, ill-natured). A tumour becomes malignant when cells migrate from the primary tumour to invade other tissues and establish colonies of secondary tumours, called metastases (Greek: meta = subsequent, stasis = location).

Depending on its origin, a tumour may be a

Strikingly, tissues and cell types capable of self renewal and derived from stem cells suffer neoplastic transformation more frequently than others. Among them, carcinomas are the most frequent tumours. Epithelia contain many dividing stem cells in which mutations may disturb the mechanisms of control. In addition, epithelia are exposed to carcinogenic agents–such as ultraviolet solar radiation–to a particularly high degree.

In cell culture cancer cells display behaviour that reveals their reluctance being controlled and they ignore social rules.