e-ISSN: 2582-5208 International Research Journal of Modernization in Engineering Technology and Science Volume:02/Issue:09/September-2020
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AN INTRODUCTION TO “SEED” AND “SOIL” HYPOTHESIS OF METASTASIS Susamman Biswas*1 *1B.Sc
(Zoology), School of Sciences(SOS), Indira Gandhi National Open University(IGNOU), Kolkata, West Bengal, India.
ABSTRACT This is a brief introduction of Seed and Soil hypothesis of Cancer Metastasis. Here I have tried to summarize the main points of Seed and Soil factors. This mechanism is mainly seen in cancer progression and colonization in an organ. But one thing need to be understood, Seed and Soil is a hypothesis as it is not found in all cases. Keywords: Cancer, Metastasis, Cytokine, EMT, MET.
I.
INTRODUCTION
Cancer has a dangerously unique feature, it spreads. That spreading is called as metastasis. Metastasis includes many features and components. Dr. Stephen Paget divided them into two categories and proposed a hypothesis. They are called as “Seed”s and “Soil”s and the hypothesis is commonly called as Seed and Soil Hypothesis [1]. This is published in 1889 and still considered as the most deserved to be true.
II.
INITIATION OF METASTASIS
Initiation of metastasis is the initiation of cancer spreading. Cells of one specific source, like malignant tumor are found in distal locations. It means cells are spreading. They travel through blood and are known as Circulating Tumor Cells(CTC). After settling down the are known as Disseminating Cancer Cells(DTC). But their source must be a malignant tumor [2]. In this spreading Seed and Soil are the most important elements.
III.
SEED IN METASTASIS
Seed is the term used to denote the sources of metastasis. Some important seed factors are as follows EMT-MET: EMT or Epithelial Mesenchymal Transition is a very hallmark feature of metastasis. To transform an epithelial cell into a mesenchymal cell many pathways, molecular factors are responsible which also promote migratory and invasive property[3][4][5][6][7][8][9][10][11][12][13]. EMT-TF or EMT Transcription Factors exhibit pleurotropic effect, which may be responsible to produce EMTs. 3 types of EMTs are found where type 1 and 2 are necessary and found during implantation, embryogenesis, organ development, tissue regeneration but type 3 is found during cancer metastasis[14][15]. MET or Mesenchymal Epithelial Transition cells are the reverse of EMT. MET is needed to colonize and EMT is present in CTC[16][17]. Cancer Stem Cell(CSC): Cancer stem cell aka Tumorigenic Cell aka Tumor Initiating Cell are the type of cell which have stem cell like properties and give birth to a tumor. It is capable of colonization[18][19][20]. Autophagy: It is not clear that how autophagy promotes metastasis, because in some cases autophagy acts pro-metastatic, e.g. caffeine induced autophagy destroys cancer cells[21][22]. Dormant Cancer Cells: Dormant cancer cells are also caller Seed factor because they can remain inactive for years. In dormant state these cells become refractory and maintain quiescence. Many genes like VCAM-1 helps them to reactivate and start metastasis[23][24]. Tumor Secreted Factors: Tumor secreted factors include extracellular vesicles, cytokines, chemokines majorly.
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Extracellular Vesicles: Cancer cells discharges more amount of exosomes than normal cells which contains DNA, RNA, Proteins and other components like hypoxia-inducible factor-1alpha which is capable to disrupt cell cell communication promoting cancer[25][26]. There are also large oncosomes present[27]. Cytokines and Chemokines: Cytokines and chemokines secreted by cancer cells activate different cell types and path- ways in nearby cells. Their primary aim is to prepare pre-metastatic niche[28]. CTC: CTC or Circulating Tumor Cells are also a great seed factor for cancer metastasis but they need to go through many mechanical, cellular, microenvironmental conditions to induce metastasis[29].
IV.
SOIL IN METASTASIS
Soil is the term used to denote the microenvironment of local area. This is the local environment and metastasis will only occur if seed and soil have great compatibility[30][31]. Two types of soils are there, they are Primary Soil Factors: Primary soil factors are the local microenvironment of the place of invasion/metastasis. They are Tumor-associated Macrophage(TAM): Tumor associated macrophages are special cells which are activated by IL4 releasing CD44 T cells. In breast cancer, they deliver miR-223, which is oncogenic by exosome mediation[32]. They also promote cancer in other organs. Mesenchymal Stem Cell(MSC): Karnoub AE et al. and Swamydas M et al. have shown that MSC within tumor enhances metastatic ability of cancer cells depend upon CCL5 signaling via chemokine receptor CCR5, Swamidas M et al. also showed that MSC plays a critical role in invasion of cancer[33][34]. Endothelial Cells: Endothelial cells of prostate cancer secrets IL6, results low AR down regulation leading to enhancing the invasion of cancer cells[35]. Carcinoma Associated Fibroblast(CAF): In breast cancer, CAFs promote breast cancer cell invasion by Wnt-planar cell polarity signaling as well as tumor growth and angiogenesis are also seen as promoted largely[36][37]. Adipocytes: In prostate cancer, miR-301a/AR/TGH- beta1/Smad/MMP9 signals are disrupted by preadipocytes, in breast cancer invasion IGFBP-2 is secreted from adipocytes[38][39]. In tumor microenvironment other cancer promoting agents are also present[40][41]. Secondary Soil Factors: Secondary soil factors are the microenvironments of distant organs which promote the metastasis and cancer colonization[42]. Colonization to a distal organ does not occur only due to malignant tumor growth, EMT- MET and other seed factors, rather they also occur due to some promoter and inducer molecules in those organs. Some are discussed as follows Lung Microenvironment: Pre-metastatic niche is suggested to be formed by recruited inflammatory chemo-attractants and myeloid cells[43]. Myeloid cells diminish the immune system by making proliferative and inflammatory microenvironment where EMT cells can be introduced easily[44][45]. Other cells like leukocytes are also involved in metastasis[46]. Liver Microenvironment: Macrophage migration inhibitory factor produced by human hepatic sinusoidal endothelial cells promotes cancer in liver[47]. Colorectal cancer progression is also supported by liver sinusoidal endothelial cell lectin expression[48]. Bone Microenvironment: MMP, CCL5 and extracellular ATP secreted by osteocytes promotes cancer invasion and growth[49]. Heterotypic adherens junctions mediates the osteogenic niche induce bone colonization of cancer[50]. Brain Microenvironment: Astrocytes are related highly with cancer induction as they can promote secretion of exosomal miRNA which creates metastatic niche[51][52]. Signals from the brain microenvironment leads to production of CCL2 in cancer cells which recruits myeloid cells and promotes metastasis[52].
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e-ISSN: 2582-5208 International Research Journal of Modernization in Engineering Technology and Science Volume:02/Issue:09/September-2020
V.
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CONCLUSION
Seed and Soil hypothesis is a very logical and most deserved to be true hypothesis. One thing is clear from the analysis of seed and soils that metastasis can occur only if proper seed and soil communication and interaction is there. So, if we can disrupt their interaction then may be we can stop spreading cancer. But that will need a lot of research work, and this paper is focused on the basic introduction of these factors to those who are enthusiasts and want to know about “Seed and Soil” hypothesis of metastasis.
ACKNOWLEDGEMENTS I acknowledge to Dr. Simranjit Singh who guided me. I want to acknowledge to Mr. Krishnendu Ghosh(MSc, FIASR) who taught me biology in a helpful and humble way. I want to acknowledge to all those researchers whose papers I have used as reference.
VI. [1] [2] [3] [4] [5] [6] [7] [8] [9]
[10] [11] [12] [13] [14] [15] [16]
[17] [18]
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