What Can We Learn from The Hormonal Mechanisms and Tumor- Inducing Bacteria That Regulate Vascular Differentiation and Cancer in Plants?

Main Article Content

Roni Aloni


Plants and human beings develop vascular tissues that enable their growth and function. Auxin (IAA) in plants, and vascular endothelial growth factor (VEGF) in humans, are the major signaling molecules that induce and regulate vascular development in both normal and cancer tissues. Mechanisms that induce vascular tissues in plants are discussed, aiming to stimulate similar advanced medical research in the human body. The focus is on organized and cancerous vascular differentiation, regulation of vein pattern formation, and the control of vessel diameter by hormonal gradients. Moreover, to understand the involvement of bacteria in cancer development in both plants and humans, for developing combined novel cancer therapy treatments in human beings with antibiotics and jasmonates.

Keywords: angiogenesis, auxin (IAA), blood vessels, cancer, cancer-inducing bacteria, jasmonate, pattern formation, tumor microbiome, vascular differentiation, vascular regeneration, vasculogensis, VEGF, Vessels

Article Details

How to Cite
ALONI, Roni. What Can We Learn from The Hormonal Mechanisms and Tumor- Inducing Bacteria That Regulate Vascular Differentiation and Cancer in Plants?. Medical Research Archives, [S.l.], v. 10, n. 7, july 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2973>. Date accessed: 25 sep. 2023. doi: https://doi.org/10.18103/mra.v10i7.2973.
Review Articles


1. Aloni R. Vascular Differentiation and Plant Hormones. Springer Nature, Cham, Switzerland 2021; ISBN: 978-3-030-53202-4
2. Tyree MT, Zimmermann MH. Xylem Structure and the Ascent of Sap. 2nd edn. Springer, Berlin 2002; ISBN-13:978-3540433545
3. Krüger-Genge A, Blocki A, Franke R-P, Jung F. Vascular Endothelial Cell Biology: An Update. Int J Mol Sci 2019; 20: 4411. Doi:10.3390/ijms20184411
4. Naito H, Iba T, Takakura N. Mechanisms of new blood-vessel formation and proliferative heterogeneity of endothelial cells. Int Immunol 2020; 32: 295–305. doi:10.1093/intimm/dxaa008
5. Ntellas P, Mavroeidis L, Gkoura S, Gazouli I, Amylidi AL, Papadaki A, Zarkavelis G, Mauri D, Karpathiou G, Kolettas E, Batistatou A. Old player-new tricks: non angiogenic effects of the VEGF/VEGFR pathway in cancer. Cancers 2020; 12: 3145. doi:10.3390/cancers12113145
6. Aloni R, Schwalm K, Langhans M, Ullrich CI. Gradual shifts in sites of free- auxin production during leaf-primordium development and their role in vascular differentiation and leaf morphogenesis in Arabidopsis. Planta 2003; 216: 841- 853. doi:10.1007/s00425-002-0937-8
7. Aloni R, Aloni E, Langhans M, Ullrich CI. Role of auxin in regulating Arabidopsis flower development. Planta 2006; 223: 315-328. doi: 10.1007/s00425-005-0088-9
8. Baylis T, Cierlik I, Sundberg E, Mattsson J. SHORT INTERNODES/STYLISH genes, regulators of auxin biosynthesis, are involved in leaf vein development in Arabidopsis thaliana. New Phytol 2013; 197: 737– 750. doi: 10.1111/nph.12084
9. Yagi H, Tamura K, Matsushita T, Shimada T. Spatiotemporal relationship between auxin dynamics and hydathode development in Arabidopsis leaf teeth. Plant Signal Behav 2021; 16: 1989216. doi: 10.1080/15592324.2021.1989216
10. Zhao Y. Essential roles of local auxin biosynthesis in plant development and in adaptation to environmental changes. Ann Rev Plant Biol 2018; 69: 417- 435. doi: org/10.1146/ annurev-arplant-042817-040226
11. Sachs T. The control of patterned differentiation of vascular tissues. Adv Bot Res 1981; 9: 151–262. doi: org/10.1016/S0065-2296(08)60351-1
12. Aloni R. Differentiation of vascular tissues. Annu Rev Plant Physiol 1987; 38: 179-204. doi: 10.1146/annurev. pp.38.060187.001143
13. Scarpella E, Helariutta Y. Vascular pattern formation in plants. Curr Top Dev Biol 2010; 91: 221-265. doi: org/10.1016/S0070-2153(10)91008-9
14. Sachs T. On the determination of the pattern of vascular tissues in pea. Ann Bot 1968; 32: 781-790. https://www.jstor.org/stable/42908089
15. Aloni R, Barnett JR. The development of phloem anastomoses between vascular bundles and their role in xylem regeneration after wounding in Cucurbita and Dahlia. Planta 1996; 198: 595-603. https://link.springer.com/article/10.1007/BF00262647
16. Mattsson J, Ckurshumova W, Berleth T. Auxin signaling in Arabidopsis leaf vascular development. Plant Physiol 2003; 131: 1327–1339. doi: 10.1104/pp.013623
17. Scarpella E. The logic of plant vascular patterning. Polarity, continuity and plasticity in the formation of the veins and of their networks. Curr Opin Genet Dev 2017; 45: 34–43. doi: org/10.1016j.gde.2017.02.009
18. Sachs T. The development of vascular networks during leaf development. Curr Top Plant Biochem Physiol 1989; 8: 168–183.
19. Aloni R, Pradel KS, Ullrich CI. The three‐dimensional structure of vascular tissues in Agrobacterium tumefaciens‐induced crown galls and in the host stems of Ricinus communis L. Planta 1995; 196: 597–605. link. springer.com/article/10.1007/BF00203661
20. Turing AM. The chemical basis of morphogenesis. Phil Trans R Soc B London 1952; 237: 37-72.
21. Wolpert L. Positional information and the spatial pattern of cellular differentiation. J Theoret Biol 1969; 25: 1-47.
22. Bhalero RP, Fischer U. Auxin gradients across wood-inductive or incidental? Physiol Plant 2014; 151: 43-51. doi:10.1111/ppl.12134
23. Aloni R, Zimmermann MH. The control of vessel size and density along the plant axis - a new hypothesis. Differentiation 1983; 24: 203-208.
24. Lüttge U. Holobionts in the Plant Kingdom. In: Progress in Botany. Springer Berlin. Heidelberg 2022; pp 1-20. doi.org/10.1007/124_2022_60
25. Ullrich CI, Aloni R. Vascularization is a general requirement for growth of plant and animal tumours. J Exp Bot 2000; 51: 1951-1960. doi: org/10.1093/jexbot/51.353.1951
26. Nejman D, Livyatan I, Fuks G, Gavert N, Zwang Y, Geller LT, Rotter- Maskowitz A, Weiser R, Mallel G, Gigi E, Meltser A, Douglas GM, Kamer I, Gopalakrishnan V, Dadosh T, Levin-Zaidman S, Avnet S, Atlan T, Cooper ZA, Arora R, Cogdill AP, Khan MAW, Ologun G, Bussi Y, Weinberger A, Lotan- Pompan M, Golani O, Perry G, Rokah M, Bahar-Shany K, Rozeman EA, Blank CU, Ronai A, Shaoul R, Amit A, Dorfman T, Kremer R, Cohen ZR, Harnof S, Siegal T, Yehuda-Shnaidman E, Gal-Yam EN, Shapira H, Baldini N, Langille MGI, Ben-Nun A, Kaufman B, Nissan A, Golan T, Dadiani M, Levanon K, Bar J, Yust-Katz S, Barshack I, Peeper DS, Raz DJ, Segal E, Wargo JA, Sandbank J, Shental N, Straussman R. The human tumor microbiome is composed of tumor type-specific intracellular bacteria. Science 2020; 368: 973–980. doi: 10.1126/science.aay9189
27. Burr TJ, Otten L. Crown gall of grape: biology and disease management. Annu Rev Phytopathol 1999; 37: 53–80.
28. Ullrich CI, Aloni R, Saeed MEM, Ullrich W, Efferth T. Comparison between tumors in plants and human beings: Mechanisms of tumor development and therapy with secondary plant metabolites. Phytomedicine 2019; 64: 153081. doi: org/10.1016/j.phymed.2019.153081
29. Van Larebeke N, Engler G, Holsters M, Van den Elsacker S, Zenen I, Schell J. Large plasmid in Agrobacterium tumefaciens essential for crown gall‐ inducing activity. Nature 1974; 252: 255–264. doi: 10.1038/252169a0
30. Chilton M, Currier T, Farrand S, Merlo D, Sciaky D, Montoya A, Gordon M, Nester E. Stable incorporation of plasmid DNA into higher plant cells: the molecular basis of crown gall tumorigenesis. Cell 1977; 11: 263–271. doi: org/10.1016/0092-8674(77)90043-5
31. Weiler EW, Schröder J. Hormone genes and crown gall disease. Trends Biochem Sci 1987; 12: 271–275. doi: org/10.1016/0968-0004(87)90133-2
32. Manulis S, Haviv‐Chesner A, Brandl MT, Lindow SE, Barash I. Differential involvement of indole‐3‐acetic acid biosynthetic pathways in pathogenicity and epiphytic fitness of Erwinia herbicola pv. gypsophilae. Mol Plant-Microbe Interact 1998; 11: 634–642
33. Thomashow MF, Hugly S, Buchholz WG, Thomashow LS. Molecular basis for the auxin‐independent phenotype of crown gall tumor tissues. Science 1986; 231: 616–618. www.jstor.org/stable/1696471
34. Zambryski P, Tempé J, Schell J. Transfer and function of T-DNA genes from Agrobacterium Ti and Ri plasmids in plants. Cell 1989; 56: 193–201. doi: org/10.1016/0092-8674(89)90892-1
35. Weiler EW, Spanier K. Phytohormones in the formation of crown gall tumors. Planta 1981; 153: 326-327.
36. Yang SF, Hoffman NE. Ethylene biosynthesis and its regulation in higher plant. Annu Rev Plant Physiol 1984; 35: 155–189.
37. Abeles FB, Morgan PW, Saltveit ME,Jr. Ethylene in Plant Biology, 2nd ed, Academic Press, San Diego, CA 2012; eBook ISBN: 9780080916286
38. Akiyoshi DE, Morris RO, Hinz R, Mischke BS, Kosuge T, Garfinkel DJ, Gordon MP, Nester EW. Cytokinin/auxin balance in crown gall tumors is regulated by specific loci in the T-DNA. Proc Natl Acad Sci USA 1983; 80: 407- 411.
39. Mattoo AK, White WB. Regulation of ethylene biosynthesis. In: The Plant Hormone Ethylene, AK Mattoo, JC Suttle (eds). CRC, Boca Raton, FL 1991; pp 21-42.
40. Cary AJ, Liu W, Howell SH. Cytokinin action is coupled to ethylene in its effects on the inhibition of root and hypocotyl elongation in Arabidopsis thaliana seedlings. Plant Physiol 1995; 107:1075-1082.
41. Aloni R, Wolf A, Feigenbaum P, Avni A, Klee HJ. The Never ripe mutant provides evidence that tumor-induced ethylene controls the morphogenesis of Agrobacterium tumefaciens-induced crown galls on tomato stems. Plant Physiol 1998; 117: 841-847.
42. Wächter R, Fischer K, Gäbler R, Kühnemann F, Urban W, Bögemann GM, Voesenek LACJ, Blom CWPM, Ullrich CI. Ethylene production and ACC‐ accumulation in Agrobacterium tumefaciens‐induced plant tumours and their impact on tumour and host stem structure and function. Plant Cell Environ 1999; 22: 1263–1273.
43. Lamb R, Ozsvari B, Lisanti CL, Tanowitz HB, Howell A, Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: treating cancer like an infectious disease. Oncotarget 2015; 6: 4569-4584. doi: 10.18632/oncotarget.3174
44. Whisner CM, Athena Aktipis C. The role of the microbiome in cancer initiation and progression: how microbes and cancer cells utilize excess energy and promote one another's growth. Curr Nutr Rep 2019; 8: 42-51. doi: org/10.1007/s13668-019-0257-2
45. Cullin N, Antunes CA, Straussman R, Stein-Thoeringer CK, Elinav E. Microbiome and cancer. Cancer Cell 2021; 39: 1317-1341. doi: org/10.1016/j.ccell.2021.08.006
46. Sepich-Poore GD, Zitvogel L, Straussman R, Hasty J, Wargo JA Knight R. The microbiome and human cancer. Science 2021; 371: 6536. doi: 10.1126/science.abc4552
47. Veselov D, Langhans M, Hartung W, Aloni R, Feussner I, Götz C, Veselova S, Schlomski S, Dickler C, Bächmann K, Ullrich CI. Development of Agrobacterium tumefaciens C58-induced plant tumors and impact on host shoots are controlled by a cascade in production of jasmonic acid, auxin, cytokinin, ethylene, and abscisic acid. Planta 2003; 216: 512-522. doi: 10.1007/s00425-002-0883-5
48. Howe GA. Jasmonates. In: Plant Hormones: Biosynthesis, Signal Transduction, Action! PJ Davies (ed). Kluwer Academic Publishers, Dordrecht, Boston 2004; pp 610-634. ISBN: 1402026854
49. Wang J, Wu D, Wang Y, Xie D. Jasmonate action in plant defense against insects. J Exp Bot 2019; 70: 3391-3400. doi: 10.1093/jxb/erz174
50. Rotem R, Heyfets A, Fingrut O, Blickstein D, Shaklai M, Flescher E. Jasmonates: novel anticancer agents acting directly and selectively on human cancer cell mitochondria. Cancer Res 2005; 65: 1984-1993. doi: 10.1158/0008-5472.CAN-04-3091
51. Goldin N, Heyfets A, Reischer D, Flescher E. Mitochondria-mediated ATP depletion by anti-cancer agents of the jasmonate family. J Bioenerg Biomembr 2007; 39: 51-57. doi: 10.1007/s10863-006-9061-y
52. Flescher E. Jasmonates in cancer therapy. Cancer Lett 2007; 245: 1-10. doi: 10.1016/j.canlet.2006.03.001
53. Zhang M, Su L, Xiao Z, Liu X, Liu X. Methyl jasmonate induces apoptosis and pro-apoptotic autophagy via the ROS pathway in human non-small cell lung cancer. Am J Cancer Res 2016; 6: 187-199. www.ajcr.us/ISSN:2156- 6976/ajcr0020320