这个时候还不需要担心害怕，因为这些细胞身上的剩下的自毁机制的“魔咒”和“镣铐”还没有完全解除。当它们的行为怪异得超过了一定的限度，轻则面临被“关”[Growth rest]，重则面临自毁机制倒计时启动[Apoptosis, 细胞凋亡]。结果是绝大部分的这类问题细胞，或或初生的癌细胞遭被斩被关的命运。
接下来还得再对另一“魔咒”，细胞老化[Senescence, or Aging]的正常程序使出杀手锏。正常的细胞按其正常的机制可以分裂大约50次左右。细胞每分裂一次，为了记住细胞分裂了多少次，上帝的安排要给细胞分裂了多少次记点，每分裂一次就，要把染色体的末端剪掉一小片段。染色体的末端虽然没有实实在在的基因成分，没有能参加编码产生蛋白质的序列，但是其长短却是决定细胞“年轻”还是“年老”非常重要的指标。细胞分裂的越多，染色体末端就变得越短。当染色体的末端短到最低限度的长度，细胞就无法再分裂了，也就是细胞老化了。这个“魔咒”对癌细胞来说那是太要命了，就算是细胞可以不死，细胞也不能无止境的分裂。
别说啊，咱细胞里面还什么都有，藏着掖着一种非常罕用的复位机制，一般只在产生生殖细胞的时候才拿出来用用。这样咱们人类和动物的下一代，才可以和亲代活差不多长的年限。这种机制可以把细胞的末端因为分裂切掉的片段重新加上或复位到上帝规定的、原来的长度。这样的机制一旦被唤醒，起作用了，那细胞就可以永远保持年轻了，再怎么分裂也没有有老化的问题了。那个失去自杀基因的癌细胞魔头，弄得整个细胞的基因组乱了套，细胞里面乱成了一团。这个管末端复位的基因，混乱的时候受某种调变机制的错误命令的启动，也出来活动了。这样癌细胞魔头就获得的超过三次以上重要的遗传调变，这个时候所谓的癌细胞，也就可以说是一个成熟的[full bloom]癌细胞了。英文称这种细胞获得了[replicative immortality]的特性，可以无限分裂，再也不受分裂次数的限制，成了不朽永生的超级细胞了。
最后一个获取的机制是途迁功能获得。本来癌细胞在一个地方生长，已经熟悉的当地的情况。一般的情况下，它们不容易搬迁到另外的不熟悉地方去生活。一旦它们获得了新的遗传改变，让他们容易在新的地方定居下来，能够在当地要钱要粮，发展壮大。这个过程称之为，浸润和转移赘生，英文称之为[invasion and metastasis]。癌细胞这个小魔头要是发展到了这一步，可以说基本上对它们没有什么好办法了。在它们还没有致人死地的情况下，它们要是不发生良性的遗传调变的话，绝大多数的情况是机体的死亡为最可能的结局。
英文：Rough Journey of Cancer Cells Ultimately Growing into a Cancer Mass
Part I: Internal Hurdles
[This article is a layman’s version of the story for an important scientific issue. If the use of analogy somehow contradicts with the latest theory, please give me your comments, we can discuss it in detail. Revised on 7-23-18.]
When we mention a cancer cell, it is indeed a terrible thing. This ‘guy’ is a real culprit, that contributes to one of the annual lethal killers and tops the list of the few among them. This time, however, I am taking the cancer cell’s stand, to present the rough journey, in a view of an easy-to-understand language, as how the cancer cell ultimately grows into a cancer mass. In the journey, the domestic or internal challenges inside the cell and the foreign threats outside of the cell come into play one after another to halter the processes. Here I would strive for the topic written in a series. This is the first article [Part I: Internal Hurdles], mainly from the cell's own genetic background or makeup, to begin with my series of the topic.
As we know, a bunch of the cancer cells are produced, and then cleared at approximately the same time, so that a cohort of army, or majority of the so-called incipient cancer cells are in play with the consequence of failure. However, being in parallel with the threats, cancer cells with somewhat of a devilish mindset, are also learning how to avoid being cleared of doom.
Let’s start from the normal data from our human body. We, the human body, have approximately 10 trillion adult cells. There are roughly 250-300 million cells per gram or cubic centimeter of either liver tissue or renal one. Every cell accommodates haploid genomic DNA bases (A, T, C, G) to as many as 3.2 billion more. It is said that with the number of 3.2 billion letters, which would be more than enough to draft equivalent to 1000 of different copies of the book of [the War and Peace]. Here we will not marvel at the mystery of the organism in that respect.
To begin with our story, it is necessary to clarify some of the basic concepts.
Cancer cell(s) could be a single cancer cell in existence, or just a few in numbers, in which its/their malignant potency is/are not very high. They could also be the cells inside the cancer mass, in which the degree of malignance reaches to the maximum level.
Cancer is a condition in which cancer cells grow to a certain degree. The body’s own defense mechanism can no longer control and confine its malignant growth, which then is called cancer.
Ten trillion normal adult somatic cells are from a single fertilized egg. It is amazing how accurate the copies of 10 trillion cells in a human body without apparent mistakes are made, so that we, normal human beings, could lead a basic healthy life. On the other hand, however, it is also impossible for all the 10 trillion cells to be without any problem at all. Although there is very low probability for the cells to become abnormal, here we would discuss it in this respect to proceed to our topic. Let us assume that we have an abnormal rate of 1 in 100 million cells. Although the abnormal rate is unimaginably low, there should be approximately 100 thousand number of the problematic cells available.
Under normal circumstances, there are a set of internal risk-proof devices in the cells. They can also be called the self-destructive devices, ‘curses’, mechanisms, or an analogy to that of the ‘lock-up’ or ‘shackles’ in figurative expression, to either destroy or confine the problematic cells. Some cells deviate from normal path of growth, or simply they are not going to be in use, they are doomed towards the journey to hell. And some of them will be quarantined until they wear away to die if they are not applicable to be completely destroyed right away. So these few amount of abnormal cells are continuously produced, killed or ‘imprisoned’ for their reasonable destiny, and thus, our normal body could function as a whole temporarily in good standing.
Our body tissues and organs are constantly in a dynamic process. Some cells will die and others more regenerate. Under normal conditions, cells generally do not grow and divide until the growth signal is applied. That means that the growth factor engages on the cell to make the cell to grow. An analogy to understand this is the way you drive your car. When one foots the gas pedal, the car starts to move. Normally, it would be important to coordinate brake and gas pedal for the speed control, in order to go fast and slow to avoid obstacles, and, alternatively, when in need of a turn. It is true that inside the cell there is also an equivalent of a brake device. It is called a growth inhibitory factor, which is responsible for timely cell adjustment of speed to make the cell to grow, neither fast nor slow, but just in perfect control.
As it is known, all the activities of cells are controlled by the genes. If some cells genetically acquire some altered changes or even mutation related to excessive growth signaling above the normal level, then the equivalent of the ‘throttle is intensified’. In addition, while the growth inhibitory factors are not timely matched up, as that of brake device is thus not effective. Or alternatively, the growth factor signaling is not escalating, and brake device is malfunctioning, therefore the car goes all the way to accelerate. The cell acquired this kind of capability(ies) or trait(s) is called the primary tumor or incipient cancer cell.
These are the first 2 genetic changes in the cell for its abnormality, although it is not necessary to happen in parallel simultaneously. Here to put it in highlighted bold form as a take-home message – GROWTH SIGHNALING increase/ GROWTH SUPPRESSOR decrease.
At this point, no real threat could be clued, because these cells have not yet liberated from all the other applied ‘curses’ and ‘shackles’. If their strange behaviors reach a certain unbearable level, they are doomed to be either escorted to the growth arrest, or to be served for the countdown start of the self-destructive mechanism for clearance.
But ah, cancer cells are the ones of little devils. They do not care about the coordination with the body tissue assigned activities. They are trying with every effort to gain in their ground in competing the body with time and numbers. The ‘die-hard revolutionary martyrs’, cancer cells die in a heroic course, but as long as they leave their fire seed available or some newly recruits join their course. They continue to make their great effort to work out a way or ways to take off the rest of the ‘curses’ and/or ‘shackles’ towards a liberation.
APOPTOSIS is a mechanism that all normal cells possess, which is a noble and great trait for an individual cell. This mechanism involves in a set of genes, which are orderly controlled for the process. While the cells are damaged or somehow something like that to critical extent, they find themselves either unable to fulfill their normal functions, either superfluous or harmful to their environment. For the sake of the body as a whole, the cells will bring this mechanism into practice and transform themselves into a so-called self-destructive program on their own for disposal. In this process, they will even be noble enough to set aside their left-over machineries to put their residuals in a ‘disposal bag’ so that no pollution to the environment will be dispersed.
The machinery of cell apoptosis is controlled by a set of genes, probably a dozen, dozens, or maybe even hundreds of different components, which come into a coordinated play to meet the purpose. One or two of the critical genes in a series become mutated or somehow lose functionality, then the whole of the mechanism will be knocked out. In doing so, these devilish cancer cells thus win a big ‘unshackling’ victory, at least they themselves are smarter than others, even if they know they are useless to the body, they could now choose not to face themselves to the miserable fate into the grave for Dutch act, or suicide, so that they could survive and continue to grow to practice their own individual living journey.
Next effort would, in turn, be made in dealing with another ‘curse’, the aging of the cells, SENESCENCE. Derailment of this program is in demand for the cancer cells to proceed freely to their course.
Normally the body cells can split about 50 times. In order to tally how many times each cell divides, in each division cycle the cell itself will cut a small piece of fragment of chromosome ends. Although the gene or protein coding region rarely sit at end of the chromosome, but its length is of vital importance to the cell to be in either younger or elder status. The more cell division the cell makes, the shorter terminal chromosome ends will become. When the terminal chromosome end is chopped to some critical length, cells are no longer dividable, and thus the aging or senescence of the cell applied. It is a trait to prevent a cell from an unlimited split.
Here is a problem. If this mechanism of cell aging or senescence is universally applied to all body cells without exception, our offspring cells will be served fewer cell division cycles as compared with that of the parent, and then all the species will ultimately be extinct from existence after a few generations.
Thank God, for us, the body is equipped with a reset machinery for use only in the germinal cell or maybe stem cell. It is amazing that this mechanism will reset our germinal cell to a time start at point 0 line. So, for our human beings and animals, the offspring can live a similar life expectancy as the parents do. This mechanism is used very rarely, normally only in germinal cell, to rebuild or refill the chromosome end to the God assigned length or original ones, so that to make the germinal cell with a new start from the very beginning.
But somehow, with the loss of gene functions in some cancer cells, they coordinate their whole genome activities in harmony into some degree of a little confusing so that a time of chaos is felt by them. By some kind of weird command, they recall this rare mechanism to render the cancer cell to this reset mechanism into play again. And now, this cancer cells become the super ones, which have already accumulated more than 3 important genetic changes mentioned above. At this point the so-called cancer cells can be said to be mature, full bloom cancer cells. Technically it is said that these cells acquire the characteristic of REPLICATIVE IMMORTALITY, they are no longer limited by the number of cell division and could theoretically replicate forever.
The last two traits, or mechanisms, that the cancer cells are in need of expedited acquisition, are the ones that are nutritional supply related, i.e. ANGIOGENESIS and INVASION and METASTASIS. When the cells simultaneously or alternatively obtain these two traits, cancer cells will reach the level of top malignancy.
Cancer cells start to grow from a very small amount into an explicit size of solid tumor, maybe not more than 2 mm in size. It will be shown that some degree of shortage of local supplies is applied just only by the diffusion of nutrients and oxygen from peripheral or adjacent blood vessels to support the consumption of the need in central part of the tumor mass. Like the construction of a new metropolis, both inside and outside of the city, a new road network for the logistical communication has to be constructed. Angiogenesis factor up -regulated following some genetic changes promotes blood vessels to sprout into the tumor mass, and to leave the mass with no corner or shaded area for necessary logistical exchanges. It likes that the road-building-up to access to any part of the ‘building’ or here solid tumors, is applied, so that every single cell in the solid tumor has no worry about shortage of ‘water, electricity, food, and essential materials’, otherwise the cell would stop growing when there would be a shortage of nutritional supply. Cancer cells at this stage would witness another big victory to have their durable colony!
In order for more colonies, the final trait the cancer cell is in need to acquire is migration and invasion, the technical term as metastasis. Initially, cancer cells are in a local growth and they get familiar with the local situation and adopt to it. Generally, it is not easy for them to migrate to another unfamiliar place to settle down. Once they get a new set of genetic alterations, which, in turn, make them easy to settle down into the new land. As soon as they settle down in the new land they are going to grab more revenues and resources for their malignant growth, like the ISIS in the real world.
Cancer cells at this stage like a successful devilish war lord now. They are now witnessing their final win with a big smile! If cancer cells develop to this stage, the human body has to admit that it basically has no good way to deal with this devilish war lord anymore. Unless some lethal genetic alteration occurs in all those cancer cells, death of the human body would be most likely the final outcome.
Of course, if the cancer cells were successful, they would just enjoy their successful endeavor for a short period of time. While they destroyed their environment, they finally had to be some heroic martyrdoms too for what they have done. However, before the cancer cells proceed to their final destiny, they are not even going to consider this doomed fate. They are wayward to enjoy completing their individual life process of fun.
To this end, we will see how the cancer cell grows into a cancer mass. It is, as a matter of the fact indeed, not an easy thing! We take a break to our story here.
To be continued!