Desmoplasia is important component in many cancers but is it essential to the process of carcinogenesis? In what manner it contributes to the progression?
In medicine, desmoplasia is the growth of fibrous or connective tissue. It is also called desmoplastic reaction to emphasize that it is secondary to an insult. Desmoplasia may occur around a neoplasm, causing dense fibrosis around the tumor, or scar tissue (adhesions) within the abdomen after abdominal surgery.
Desmoplasia is usually only associated with malignant neoplasms, which can evoke a fibrosis response by invading healthy tissue.
In other words, the body reacts similarly to a cancer as it does to a wound, causing scar-like tissue to be built around the cancer. As such, the surrounding stroma plays a very important role in the progression of cancer. The interaction between cancer cells and surrounding tumor stroma is thus bidirectional, and the mutual cellular support allows for the progression of the malignancy.
Desmoplasia is thought to have a number of underlying causes. In the reactive stroma hypothesis, tumor cells cause the proliferation of fibroblasts and subsequent secretion of collagen.The newly secreted collagen is similar to that of collagen in scar formation – acting as a scaffold for infiltration of cells to the site of injury. Furthermore, the cancer cells secrete matrix degrading enzymes to destroy normal tissue ECM thereby promoting growth and invasiveness of the tumor. Cancer associated with a reactive stroma is typically diagnostic of poor prognosis.
The tumor-induced stromal change hypothesis claims that tumor cells can dedifferentiate into fibroblasts and, themselves, secrete more collagen. This was observed in desmoplastic melanoma, in which the tumor cells are phenotypically fibroblastic and positively express genes associated with ECM production. However, benign desmoplasias do not exhibit dedifferentiation of tumor cells.
While scars are associated with the desmoplastic response of various cancers, not all scars are associated with malignant neoplasms.
Benign Condition Examples
1. Desmoplastic melanocytic naevus
2. Desmoplastic spitz naevus
3. Desmoplastic cellular blue naevi
4. Desmoplastic hairless hypopigmented naevus
5. Desmoplastic trichoepithelioma
6. Desmoplastic trichilemmoma
7. Desmoplastic tumor of the follicular infundibulum
8. Sclerotic dermatofibroma
9. Desmoplastic fibroblastoma
10. Desmoplastic cellular neurothekeoma
11. Sclerosing perineurioma
12. Microvenular haemangioma
13. Immature scars
Malignant Condition Examples
1. Desmoplastic malignant melanoma
2. Desmoplastic squamous cell carcinoma
3. Morpheaform basal cell carcinoma
4. Microcystic adnexal carcinoma
5. Cutaneous leiomyosarcoma
6. Cutaneous metastasis
Prostate Cancer
Breast Cancer
Desmoplasia is usually associated with malignant tumors, which can evoke a fibrosis response by invading healthy tissue. Scar-like tissue were built around the cancer. As such, the surrounding stroma plays a very important role in the progression of cancer.
In particular, pancreatic and liver cancers are associated with severe fibrosis, desmoplasia. TGF-beta signal activation and the sequent increased number of myofibroblasts positive for alpha-SMA induces desmoplasia in pancreas, often referred to as pancreatic fibrosis. In the case of hepatic cancer, Ito cells, which usually store vitamin-A, are responsible for the trnsdifferentiation into alpha-SMA(+)myofibroblasts and induces the cirrhosis, the severe fibrosis in the liver.
In general, fibrosis is not only the cause but also the result of carcinogenesis. Desmoplasia-induced tumor tissues have stiff stroma, thus the tumor-associated vessels are collapsed so that the treatment targeting collagen composed of stiff stroma has a promising effect.
Desmoplasia is the growth of fibrous or connective tissue. It is also called desmoplastic reaction to emphasize that it is secondary to an insult. Desmoplasia may occur around a neoplasm, causing dense fibrosis around the tumor or scar tissue (adhesions) within the abdomen after abdominal surgery.
Desmoplasia is usually only associated with malignant neoplasms, which can evoke a fibrosis response by invading healthy tissue. Infiltrating metastatic ductal carcinomas of the breast often have a scirrhous, stellate appearance caused by desmoplastic formations.
Cancer begins as cells that grow uncontrollably, usually as a result of an internal change or oncogenic mutations within the cell. Cancer develops and progresses as the microenvironment undergoes dynamic changes. The stromal reaction in cancer is similar to the stromal reaction induced by injury or wound repair: increased ECM and growth factor production and secretion, which consequently cause growth of the tissue. In other words, the body reacts similarly to a cancer as it does to a wound, causing scar-like tissue to be built around the cancer. As such, the surrounding stroma plays a very important role in the progression of cancer. The interaction between cancer cells and surrounding tumor stroma is thus bidirectional, and the mutual cellular support allows for the progression of the malignancy.
In medicine, desmoplasia is the growth of fibrous or connective tissue. It is also called desmoplastic reaction to emphasize that it is secondary to an insult. Desmoplasia may occur around a neoplasm, causing dense fibrosis around the tumor, or scar tissue (adhesions) within the abdomen after abdominal surgery.
Desmoplasia is usually only associated with malignant neoplasms, which can evoke a fibrosis response by invading healthy tissue.
In other words, the body reacts similarly to a cancer as it does to a wound, causing scar-like tissue to be built around the cancer. As such, the surrounding stroma plays a very important role in the progression of cancer. The interaction between cancer cells and surrounding tumor stroma is thus bidirectional, and the mutual cellular support allows for the progression of the malignancy.
Desmoplasia is thought to have a number of underlying causes. In the reactive stroma hypothesis, tumor cells cause the proliferation of fibroblasts and subsequent secretion of collagen.The newly secreted collagen is similar to that of collagen in scar formation – acting as a scaffold for infiltration of cells to the site of injury. Furthermore, the cancer cells secrete matrix degrading enzymes to destroy normal tissue ECM thereby promoting growth and invasiveness of the tumor. Cancer associated with a reactive stroma is typically diagnostic of poor prognosis.
The tumor-induced stromal change hypothesis claims that tumor cells can dedifferentiate into fibroblasts and, themselves, secrete more collagen. This was observed in desmoplastic melanoma, in which the tumor cells are phenotypically fibroblastic and positively express genes associated with ECM production. However, benign desmoplasias do not exhibit dedifferentiation of tumor cells.
While scars are associated with the desmoplastic response of various cancers, not all scars are associated with malignant neoplasms.
Benign Condition Examples
1. Desmoplastic melanocytic naevus
2. Desmoplastic spitz naevus
3. Desmoplastic cellular blue naevi
4. Desmoplastic hairless hypopigmented naevus
5. Desmoplastic trichoepithelioma
6. Desmoplastic trichilemmoma
7. Desmoplastic tumor of the follicular infundibulum
8. Sclerotic dermatofibroma
9. Desmoplastic fibroblastoma
10. Desmoplastic cellular neurothekeoma
11. Sclerosing perineurioma
12. Microvenular haemangioma
13. Immature scars
Malignant Condition Examples
1. Desmoplastic malignant melanoma
2. Desmoplastic squamous cell carcinoma
3. Morpheaform basal cell carcinoma
4. Microcystic adnexal carcinoma
5. Cutaneous leiomyosarcoma
6. Cutaneous metastasis
Prostate Cancer
Breast Cancer
The mechanisms of extracellular excessive shift balance anabolic & catabolic processes into excessive anabolic endoergonic processes of fibrous / connective tissue leading to intensive growth of this tissue around cancer tumor which is named Desmoplasia. I think that this mechanism is touched also on tumor angiogenesis via fibronectins, proteoglycins, tenascun-C and other proteins providing aerobic oxidation for tumor cells survival in condition of prevailing glycolysis due to AKT/PI3K and HIF-1 operation in cancer tissue. Thus Warburg effect of aerobic glycolysis occurs in metabolism of some cancer tissue. However the similar processes inducing by similar mechanisms occur less intensively in the other cancer tissue due to v-oncogene property or cancer cells / tissue characteristic of metabolism, i.e. quantity of fibroblasts etc. Just these cancer tissues don't show intensive growth of tissue around cancer tumor which is named Desmoplasia.
Dear Mr. Adil H.H. Bashir,
These are the explanation mechanism of Desmoplasia which answer to your first query:
The mechanisms of extracellular excessive shift balance anabolic & catabolic processes into excessive anabolic endoergonic processes of fibrous / connective tissue leading to intensive growth of this tissue around cancer tumor which is named Desmoplasia. I think that this mechanism is touched also on tumor angiogenesis via fibronectins, proteoglycins, tenascun-C and other proteins providing aerobic oxidation for tumor cells survival in condition of prevailing glycolysis due to AKT/PI3K and HIF-1 operation in cancer tissue. Thus Warburg effect of aerobic glycolysis occurs in metabolism of some cancer tissue. However the similar processes inducing by similar mechanisms occur less intensively in the other cancer tissue due to v-oncogene property or cancer cells / tissue characteristic of metabolism, i.e. quantity of fibroblasts etc. Just these cancer tissues don't show intensive growth of tissue around cancer tumor which is named Desmoplasia.
Desmoplasia in cancer metabolism depends either on v-oncogene property or on cancer cells / tissue characteristic of metabolism. Thus Desmoplasia reflects only activity v-oncogene and metabolic property of both cancer cells and cancer connective tissue. This is the answer to your second query.
Dear Dr. Mohit Sharma,
Indeed Desmoplasia is essentially to the intensive process of extracellular carcinogenesis in connective tissue which is subjected to intensity of cellular processes mutation in some tissues and in some conditions. As concerning to second your query [In what manner it contributes to the progression?] I think that expression Desmoplasia characterizes intensity of angiogenesis of cancer tumor, i.e. expression extracellular processes exerting cancer development.
In addition, I am sorry but I must notify that I shall be awaiy from 20.02.2015 to 26.03.2015.
Sincerely yours,
Dr. M.Ponizovskiy
Dear Dr. Mohit Sharma,
Already I answer yours two queries (see above). Now I want to repeat that I shall be away from 20.02.2015 till 26.03.2015.
Sincerely yours,
Dr. M.Ponizovskiy
Dear Dr. Mohit
Khalid O. Alfarouk1, Daniel Verduczo2, Cyril Rauch3, Abdel Khalig Muddathir1,
Adil H. H. Bashir1, Gamal O. Elhassan4,5, Muntaser E. Ibrahim1, Julian David Polo
Orozco6, Rosa Angela Cardone7, Stephan J. Reshkin7 and Salvador Harguindey6. Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question. www.impactjournals.com/oncoscience Oncoscience, Advance Publications 2014.
Hope you find some answers to questions you raised.
Thanks Dr Michail R Ponizovskiy for informations you add.
Hope you revise Dr Khalid O. Alfarouk.
Dear Dr. Adir H.H. Bashir,
I am grateful you for the interesting article entitled "Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question" which was published by Khalid O., Alfarouk with you. I value this work to rate high. However unfortunately the authors of this work have inclined their explanation mechanism of Warburg effect to the increase of PH and excessive Lactic acid and did not elucidate difference energy flows via anabolic pathway and catabolic pathway in normal metabolism and in cancer metabolism which exlains difference of resisted pathways between Warburg effect [aerobic glycolysis] in cancer metabolism and Pasteur effect [incompatibility of glycolysis (increase Lactic acid) and aerobic oxidation] in normal metabolism. Just the explanation difference between Warburg effect and Pasteur effect was the main special feature of Warburg theory, which the authors of the article did not throw light upon it. Therefore the authors have noted "The errors and limitations of Otto Warburg's theory" quite wrondfully. Thus I consider that the elucidated mechanism of Warburg effect in this interesting work was insufficient. Please, see the other explanation mechanism of Warburg effect which is based on the first law of thermodynamic of stability Internal Energy of Stationary State normal organism and Quaei-stationary State of cancer disease:
*Ponisovskiy M.R., (2010), “Cancer metabolism and the Warburg effect as anabolic process outcomes of oncogene operation”, Critical Reviews in Eukaryotic Gene Expression, 20 (4), 325 – 339;
*Ponizovskiy M.R., (2013), Biophysical and biochemical transmutation of mitochondrial function in cancer genesis, Biochemistry & Analytical Biochemistry, Volume 2, Issue 3, doi:10.4172/2161-1009.1000137;
*Ponizovskiy M.R., (2013), Biophysical and biochemical models of cellular development mechanisms via cellular cycle as in normal tissue and as well as in cancer tissue and in inflammatory processes, Critical Reviews in Eukaryotic Gene Expression, 23 (2), 171 – 193;
*Ponizovskiy M., (2014), The mechanisms operation of thermodynamic system of a human organism, European Journal of Biophysics, 2 (4), 29 – 37, doi: 10.11648/j.ejb.20140204.11.
Dear Ponizovskiy, thank you very much form very scientific comment which deserve revision and more discussion for me and my author and other colleagues. I promise you the author and us will make contact together to reach more benefit for research and science.
Talking about desmoplasia and cancer, desmoplasia might be a double-edged sword. While some scientists are focusing on its invasive capacity of the fibrous tissue on the neighboring tissues, others are instigating on its role in encapsulated tumors.
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