Paget's “seed and soil” theory explained ..
In 1889, Dr. Stephen Paget proposed the "seed and soil" hypothesis, which states that cancer cells (the seeds) need the proper microenvironment (the soil) for them to grow, spread and metastasize systemically. In this hypothesis, Dr. Paget rightfully recognized that the tumor microenvironment has an important role to play in cancer progression and metastasis. In this regard, a series of recent studies have elegantly shown that the production of hydrogen peroxide, by both cancer cells and cancer-associated fibroblasts, may provide the necessary "fertilizer," by driving accelerated aging, DNA damage, inflammation and cancer metabolism, in the tumor microenvironment. By secreting hydrogen peroxide, cancer cells and fibroblasts are mimicking the behavior of immune cells (macrophages/neutrophils), driving local and systemic inflammation, via the innate immune response (NFκB). Thus, we should consider using various therapeutic strategies (such as catalase and/or other anti-oxidants) to neutralize the production of cancer-associated hydrogen peroxide, thereby preventing tumor-stroma co-evolution and metastasis. The implications of these findings for overcoming chemo-resistance in cancer cells are also discussed in the context of hydrogen peroxide production and cancer metabolism.
define Paget's seed and soil hypothesis of metastasis
The greatest ancient nation took the longest time to develope its iron power; the securest political freedom in a nation did not advance by bounds, or by violent revolutions, but in England "broadened slowly down from precedent to precedent." The greatest modern society — the Church of Christ — grew as Christ prophesied, from a beginning as small as a grain of mustard seed into a noble tree, and grows now more slowly than other society has ever grown — so slowly, that persons who are not far-seeing say that it has failed.
All the greatest triumphs of human art and skill have been lately collected in the Exhibitions of London and Paris; but if all the mechanics who made these, and all the learned men in the world were united, and if they were to work together for a thousand years, they could not form one living grain of corn, one seed of a living poppy, one seed of any kind, containing within it, infolded in the germ, ten thousand plants of corn, or one hundred thousand plants of poppies, proceeding from and succeeding each other from this time till the end of the world.()
The “seed and soil” hypothesis revisited - The Lancet Oncology
Stephen Paget proposed the "seed and soil" hypothesis, which states that cancer cells (the seeds) need the proper microenvironment (the soil) for them to grow, spread and metastasize systemically.
The “seed and soil” hypothesis revisited
First invoked by Paget, the seed and soil hypothesis suggests that the successful growth of metastatic cells depends on the interactions and properties of cancer cells (seeds) and their potential target organs (soil). In the context of the seed and soil hypothesis this review examines recent advances in the understanding of molecular and cellular features that permit transformed epithelial cells to gain access to the blood stream (intravasation), survive their journey through the blood stream, and ultimately traverse through the microvasculature of target organs (extravsation) to deposit, survive, and grow in a foreign tissue environment. In addition to a review of the clinical and experimental evidence supporting the seed and soil theory to cancer metastasis, additional concepts highlighted include: (i) The role of cancer stem-like cells as putative cells of metastatic origin (the “seeds”); (ii) the mechanism of epithelial to mesenchymal transition (EMT) in driving epithelial cell conthose molecules do no blood stream to avoid anoikis, or anchorage independent cell death; and (iv) the reverse process of EMT, or mesenchymal to epithelial transition (MET), which promotes conversion back to the parent cell morphology and growth of macrometastsis in the target organ. The unique biology of metastases once established in the brain, and in particular the “sanctuary” role that the brain microenvironment plays in promoting metastatic growth and treatment resistance, will also be examined. These issues are of more than academic interest since as systemic therapies gradually improve local tumor control, the relative impact of brain metastasis will inexorably play a proportionally greater role in determining patient morbidity and mortality.
The Cancer Seed and Soil Hypothesis
Since Paget's first description of the seed and soil hypothesis regarding cancer metastasis in 1889, there has been much debate and investigation into the factors that ultimately drive metastatic deposits into their ultimate locations. Put briefly, the seed and soil hypothesis maintains that cancer cells (the seed) metastasize to locations that are biochemically and physiologically favorable for implantation and growth. Given that the cause of death for most patients with cancer is the development of disseminated cancer, the understanding of metastasis is an essential prerequisite to developing novel therapeutic strategies that will significantly impact patient outcomes.