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The Surface Properties of Cancer Cells: a Review

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The Surface Properties of Cancer Cells: a Review The Surface Properties of Cancer Cells: A Review Al. ABERCROMBIEANDE. J. AMBROSE (University College; and Chester Realty Research Institute, Institute of Cancer Research, London, England) BIOLOGICALASPECTS 525 3. Disorganization. The malignant cells as they Local invasiveness 525 multiply fail to form tissue of the arrangement Metastasis 532 characteristic of their normal counterparts. Disorganization 532 4. Persistent growth. The malignant cell popu Growth and Mitosis 532 lation keeps up a continuous growth by mitosis. Conclusions 532 PHYSICALASPECTS 534 LOCAL INVASIVENESS Adhesivenessof Normal and Tumor Cells . 534 Mechanisms of cellular locomotion .... 539 We must first consider what is the mechanism ITltrastructure of cell contacts 541 of movement of malignant cells when they invade their immediate surroundings. Probably the main Biochemicalproperties oftumor cellmembranes 543 mechanism is active "amoeboid" cell locomotion, In recent years attention has been increasingly which was first recorded for cancer cells nearly a turning to the cell surface as the seat of an impor century ago. Since the advent of tissue culture it tant part of the malignant transformation. This has been observed in a very wide range of meta- widening of the field of interest of cancer workers zoan cells. Until the mechanics of this style of owes its beginning largely to the work of Coman locomotion are better understood it seems prefer (34). Coman was concerned with how invasion and able to put the term "amoeboid" to one side and metastasis occur, and this crucial aspect of the to use the relatively noncommittal name "solid- cancer problem—crucial in the sense that it con substrate locomotion." This emphasizes one essen cerns the difference between benign and malignant tial aspect of the mechanism : it involves adhesion, growth-—must still be the main preoccupation of though transient at any one point, to a solid sub a review on the cell surface in relation to cancer. strate. Only flagellated (or ciliated) cells can swim. Other aspects may, however, be linked together in The necessity for a substrate makes the nature of a speculative way, and to these we will refer brief the cell surface, and of the surrounding solid struc ly. The review is divided into two main sections: tures with which the cell surface comes into con (a) a discussion of the biological evidence for the tact, of profound importance for locomotor be existence of surface peculiarities of malignant cells havior. (M.A. has been responsible for this section) ; (6) a A number of pathologists (e.g., Willis [146], discussion of the physical evidence as to what the Young [150]) consider that the pressure developed surface peculiarities may be (E.J.A. has been re within a tumor by its growth provides the main sponsible for this section). motive power for invasion. The peripheral malig nant cells, according to this view, are forced along BIOLOGICAL ASPECTS paths of lesser resistance through the surrounding tissues, disrupting their structure and so inter The deviations from normal of malignant cells mingling with the normal cells. It may be recalled, can conveniently be discussed, from the point of however, that Wolff (147, 148) and his colleagues view of the cell surface, in the following categories. have shown that, when a malignant tumor is laid 1. Local invasion. The malignant cells move against an organ in culture, invasion of the latter outward from the focus of origin of the neoplasm, occurs. In these circumstances it seems inconceiv insinuating themselves amongst the surrounding able that the growing tumor can exert any pres normal cells. sure. We shall, therefore, concentrate on active 2. Metastasis. As a result of invasion the malig locomotion, though it is not, of course, justifiable nant cells reach moving body fluids, by which they to conclude that passive transport by means of are passively transported and become widely dis pressure in no circumstances contributes to in seminated. vasion. 525 Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 1962 American Association for Cancer Research. 526 Cancer Research Vol 22, June 1962 THE NONINVASIVESTATE reaction was demonstrated by Abercrombie and The capacity to perform solid substrate locomo Heaysman (7), who investigated the interactions tion is certainly observed among the majority of of chick heart fibroblasts moving in liquid medium kinds of malignant cells when they are cultured in culture on a glass surface. Interaction was obtained vitro (see for instance Coman [35]). However, it is by placing two primary expiants about 1 mm. also found among the majority of kinds of normal apart. The movement and the distribution of the cells of a vertebrate; red cells and germ cells are cells, before and after the outgrowth from the two the most obvious exceptions. The mere existence expiants made contact with each other, were meas of an orderly pattern of cells in the body makes ured. It was found that, as soon as a complete it, however, impossible to believe that, in normal junction had been established between the two circumstances, adult cells (white blood cells are outgrowths, but not before, the cells showed a an exception) undertake extensive locomotion of an change of behavior: their speed dropped sharply, invasive kind—i.e., involving penetration among their direction of movement became random in other normal cells. Direct evidence as to whether, stead of predominantly outward from the expiant, and if so in what circumstances and how far, nor and the density of population in the inter-explant mal adult cells move in vivo is of course hard to region became almost stable. The cells between the achieve, and there may be an unsuspected amount expiants, in fact, largely ceased moving, undergo of small-scale movement. Nevertheless, it seems ing apparently mere oscillations; and they re safe to suppose that the problem of invasiveness mained distributed on the glass surface, if not in is as much a question of why normal cells stay sub a perfect monolayer, at least with far fewer over stantially in place as of why malignant cells do laps than was to be expected had they been dis not. We will, therefore, consider some ideas as to posed at random without mutual interference. No why a normal adult cell (other than a white blood slowing of movement before junction of the two cell) does not move extensively among other nor outgrowths was detectable. It was, therefore, con mal cells, even though it has the power of locomo cluded that the cells were inhibiting one another tion, under two headings: (a) mutual inhibition of by mutual contact of cell surfaces, and the phe movement by contact ("contact inhibition"); (6) nomenon was termed contact inhibition. A similar other hypotheses of locomotor inactivation. quantitative analysis was applied to the interac Contact inhibition.—It is a well known principle tion of fibroblasts from chick embryo heart with that "epithelium will not tolerate a free edge." those from neonatal mouse skeletal muscle, and Given a suitable substrate, a free edge will advance they were found to inhibit each other in the same by movement of the epithelial sheet behind it. The way by contact (8). idea is of long standing that the movement of such The cytological details of what happens during a sheet is stopped by contact of its edge with an contact inhibition of fibroblasts were studied by other epithelial edge, because this abolishes the Abercrombie and Ambrose (4). They found that polarization of the peripheral cells between the usually, when a fibroblast made contact with a free space in front of them and their followers be second one, the ruffled membrane that forms the hind them (see Arey [21]). As early as 1913 Smith leading edge of the first fibroblast joins closely to (124) examined the interaction of different epi- the second cell, at the same time ceasing its un thelia from this point of view. Perhaps most im dulations. When the leading ruffled membrane is portant for the present review is the quantitative immobilized in this way, the cell bearing it ceases study by Lash (95) of the movement of epidermis to move in the original direction. The region of over skin wounds in amphibian larvae. By marking contact between two cells, judging from microdis individual cells he was able to show that, after section studies (94) and from the distortion pro excision of a small piece of skin, a rim of epidermis duced in the pair of cells when renewed locomotion around the wound takes part in the movement and in another direction draws them apart again until that there is a rather abrupt cessation of move they separate with a sudden recoil (6), is as a rule ment throughout this rim when the free edges meet a firm but not indissoluble adhesion between the in the middle of the wound. There remains an two plasma membranes. Some of these observa important obscurity about such epithelial move tions have been substantially confirmed by Weiss ment, as to how cells behind the free edge move (142). appropriately; but the cells at the edge seem to be The nature of the inhibitory effect of contact the pacemakers, and their movement seems to be between fibroblasts is unknown. There are various controlled by the state of their contacts with other hypotheses at present under consideration (3, 18, cells. 40), according to which a change in a contacting That fibroblasts have a similar sort of contact cell may be produced; such a change can then Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 1962 American Association for Cancer Research. ABERCROMBIEANDAMBROSE—SurfacePropertiesof Cancer Cells 527 provide the basis for an alteration in locomotion, additional mechanisms, and how far the cell sur (a) The cell may in some way be paralyzed by the face may be involved in them.
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