I imagine there is stress exerted on blood vessel walls as the cell volume increases, but I am not sure.

Tumour growth is accompanied by neoangiogenesis. The new capillaries arise from venules and not capillaries unlike normal tissue. Depending on the grade of malignancy, a tumour can 'outgrow' it's blood supply which results in necrotic death of many cells which contributes to cell loss. The decreased blood supply also slows down the overall growth rate of the tumour.

Since the blood suply is from venules, it can be presumed that the fluid pressure per se will be less than in normal tissue. But the overall pressure inside a tumour is likely to be higher in view of the increased cell number expansion. On that basis, the pressure inside a tumour will lessen (or rather rate of increase will be lesser) if the cell number does not increase.

But I cant imagine why a tumour should stop growing other than due to decrease in blood supply; ie it is the decrease pressure that decreases tumour growth. Of course, some hormone dependent tumours may decrease growth rate for other reasons.

Narayanan

Dear Mohith

1. " I stress on word abberant as is highly unusual to consider vasculature in tumor as normal ". I never termed vasculature in tumour as normal! In fact I stressed it's aberrancy by stating that in tumours new capillaries arise from venules.

2. The primary event in a tumour is cell growth, and I would say that this is the main event that leads to alteration in any pressure changes. As tumours increase in size, or tumour cells increase in number, there will be changes in fluid pressure which alters tumour kinetics, especially deep inside a solid tumour. There is cell death too following lack of oxygen, nutrition, etc. And a lot of sludging.

3. You say that " and the reasons elevated interstial fluid pressure is abberant angiogenesis and abberant lymphangiogenesis ". May I remind you that the reason for the angiogenesis is secretion of Vascular endothelial growth factor (VEGF) secreted by tumour cells, and this is why anti-VEGF drugs are in the forefront of anti-cancer research! Therefore, technically, you yourself agree that it is the tumour growth that causes alteration in fluid pressure. In slow growing tumours, there is enough time for angiogenesis too, and less chance of necrosis and ulceration.

4. What I said is " But the overall pressure inside a tumour is likely to be higher in view of the increased cell number expansion." Of course this includes interstitial fluid pressure.

5. Let us take your advice about reading up on the literature.

Take this article for instance: Article Estimation of Tumor Interstitial Fluid Pressure (TIFP) Noninvasively

Of course you have to bee harsh when dealing with imbecile students; and we are all students for our whole life, isnt it?

Narayanan

Everything started with the proliferation of the tumor cells, and depends on their inherent aggressiveness. This is the horse!

Initially itself I had noted that after a tumor has developed, changes in its vascularity will alter it's growth rate, may be it's nature too. Tying up the vessels to a tumor has been tried as a treatment modality too! Changes in ifp is but secondary to interference with vascularity.

Pressure is force per unit area. And it is secondary to many things that can alter it. In any tissue, the main factors are the pressure of the blood supply, capillary permeability, cell proliferation, etc. The pain you feel in an abscess is due to increased pressure due to cell proliferation, but there is lot of cell death too. Ifp in an abscess too will be increased.

A tumor gets supply from a particular artery. Whatever be the number of new capillaries laid down by the tumour, the blood supply is not going to increase since no new arteries are formed. Of course, the edges may get more blood from vessels, some of which may be from another artery. This is why necrosis occurs in the centre.

Narayanan

I am a radiotherapist and as you are aware Radiotherapy is intimately concerened with tumour vascularity, hypoxia, cellular microenvironment, etc. Don't think that as you suggested I am unaware of these. IA glane at my papers will reveal that it is not so. I have worked in the Gray lab too, and dealt with radiomodofoers that are related to altering tumour microenviron ment.

There are very very many tests to assess vascularity and IFP is but one of them. But these measurements, including fibroblasts etc., serve as at the best signs of prognosis and radio/chemosensitivyty and are not factors, where as tumour cell proliferation is the true factor.

Please do look up a person's biodata in the profile brfore branding him as an ignorant person.

Now and then laboratory researchers come up with fancy tests which they hope will serve some superior purpose; but most often they will not, because they are not real factors.

Narayanan

Dear Mohith

I never said that the effect is unidirectional. From my first answer onwards, I have been noting that change in blood supply influences tumour growth rate, and has noted it again and again. One parameter to measure this is tumour oxygenation, directly or indirectly. IFP is just another parameter. But the prime factor determining both is the aggressiveness of the tumour. And the tumour vessels are like as you described because the new capillaries are formed from venules, and not from arterioles.

Other than tumour growth rate,other factors too can affect oxygenation, IFP etc. For example, pressure on a supply vessel, by the tumour itself or other cause. If we tie up the vessel, it can alter IFP as well as tumour oxygen, as well as many other parameters.

IFP and the others are just signs where as tumour cell number, growth rate etc., are both signs as well as factors determining prognosis, radioresistance, etc.

Narayanan

You can approach the issue in another way. Suppose someone finds out that the IFP is best indicator of prognosis/radiosensitivity; ie it is the best sign of prognosis, what can you do about it? Try to alter the IFP? And how can one alter the IFP? Only by altering the blood supply or altering the growth rate, isn't it?

Narayanan

One more thing. Every Radiotherapist has to study Radiobiology, and tumour microenvironment is part of this.knowledge of The 4 Rs of radiotherapy are Repopulation, Redistribution, Reoxygenation and Repopulation, and these are heavily affected by tumour environment.

Your area of interest may be IFP, tumour matrix, etc. If you are lucky to find a way to control these other than tumour cells directly or vascularity, it may benefit, something like Bevacizumab which inhibits VEGF.

Wish you all luck.

Narayanan

Thank you🙏