Revisiting Seed and Soil: Examining the Primary Tumor and Cancer Cell Foraging in Metastasis

Groot, Amber E. de; Roy, Sounak; Brown, Joel S.; Pienta, Kenneth J.; Amend, Sarah R.

doi:10.1158/1541-7786.mcr-16-0436

Cited by 82 publications

(87 citation statements)

References 71 publications

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“…In modern cancer biology, it is well accepted that metastatic spread is a stochastically rare event; the overwhelming majority of cells that leave the primary tumor will not establish a secondary tumor . Likewise, we also know that patients with metastatic disease, even with an initial response to systemic therapy, will eventually fail and their disease will recur.…”

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confidence: 99%

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Polyploid giant cancer cells: Unrecognized actuators of tumorigenesis, metastasis, and resistance

et al. 2019

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Cancer led to the deaths of more than 9 million people worldwide in 2018, and most of these deaths were due to metastatic tumor burden. While in most cases, we still do not know why cancer is lethal, we know that a total tumor burden of 1 kg—equivalent to one trillion cells—is not compatible with life. While localized disease is curable through surgical removal or radiation, once cancer has spread, it is largely incurable. The inability to cure metastatic cancer lies, at least in part, to the fact that cancer is resistant to all known compounds and anticancer drugs. The source of this resistance remains undefined. In fact, the vast majority of metastatic cancers are resistant to all currently available anticancer therapies, including chemotherapy, hormone therapy, immunotherapy, and systemic radiation. Thus, despite decades—even centuries—of research, metastatic cancer remains lethal and incurable. We present historical and contemporary evidence that the key actuators of this process—of tumorigenesis, metastasis, and therapy resistance—are polyploid giant cancer cells.

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confidence: 99%

“…To better understand cancer, tumors may be described and modeled as ecosystems, with cancer cell species coexisting in a complex habitat with host cell species . The cancer cells, the body's normal cells, and the tumor microenvironment in which they reside and influence make up the cancer ecosystem.…”

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Polyploid giant cancer cells: Unrecognized actuators of tumorigenesis, metastasis, and resistance

et al. 2019

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“…the stroma, seems to be responsible for the malignant progression of tumors by allowing or restricting cancer cells to migrate out of the primary tumor into the tumor stroma. [16][17][18][19][20] Thus, the stroma has two faces: a driving force for cancer cell motility 3,9,21,22 and a steric obstacle hindering cancer cell migration through this special type of connective tissue. 22,23 In addition, the migration of cells can be of different types: single-cell migration or collective migration, such as sheet migration.…”

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The two faces of enhanced stroma: Stroma acts as a tumor promoter and a steric obstacle

et al. 2017

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In addition to genetic, morphological and biochemical alterations in cells, a key feature of the malignant progression of cancer is the stroma, including cancer cell motility as well as the emergence of metastases. Our current knowledge with regard to the biophysically driven experimental approaches of cancer progression indicates that mechanical aberrations are major contributors to the malignant progression of cancer. In particular, the mechanical probing of the stroma is of great interest. However, the impact of the tumor stroma on cellular motility, and hence the metastatic cascade leading to the malignant progression of cancer, is controversial as there are two different and opposing effects within the stroma. On the one hand, the stroma can promote and enhance the proliferation, survival and migration of cancer cells through mechanotransduction processes evoked by fiber alignment as a result of increased stroma rigidity. This enables all types of cancer to overcome restrictive biological capabilities. On the other hand, as a result of its structural constraints, the stroma acts as a steric obstacle for cancer cell motility in dense three-dimensional extracellular matrices, when the pore size is smaller than the cell's nucleus. The mechanical properties of the stroma, such as the tissue matrix stiffness and the entire architectural network of the stroma, are the major players in providing the optimal environment for cancer cell migration. Thus, biophysical methods determining the mechanical properties of the stroma, such as magnetic resonance elastography, are critical for the diagnosis and prediction of early cancer stages. Fibrogenesis and cancer are tightly connected, as there is an elevated risk of cancer on cystic fibrosis or, subsequently, cirrhosis. This also applies to the subsequent metastatic process.

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“…The metastatic properties of tumor cells were extensively investigated from 1970s, although so much earlier (as soon as 1889) it was proposed the “seed an soil” theory that today is still alive and even under constant reformulation ( e.g .,[65])…”

Section: Genometastasis: a Putative Mechanism Involved In The Originmentioning

confidence: 99%

“…On the whole, it might be said that the discussion of “dynamic heterogeneity” models vs “clonal dominance” theories prevailed during two decades, always under the premise of a circulatory view of cancer progression. In fact, nowadays, many authors appears to not conceive any other way, as showed in the recent literature, e.g ., “Metastasis is the consequence of a cancer cell that disperses from the primary tumor, travels throughout the body, and invades and colonizes a distant site”[65]. …”

Section: Genometastasis: a Putative Mechanism Involved In The Originmentioning

confidence: 99%

Further the liquid biopsy: Gathering pieces of the puzzle of genometastasis theory

García-Casas

García‐Olmo

Garcı́a-Olmo

2017

WJCO

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Metastasis is the major cause of mortality in cancer disease and still constitutes one of the most controversial mechanism, not yet fully understood. What is almost beyond doubt is that circulatory system is crucial for cancer propagation. Regarding this system, much attention has been recently paid to liquid biopsy. This technique is aimed to detect circulating tumor cells (CTCs) and circulating nucleic acids so it can be used as a tool for diagnostic, prognostic and follow-up of patients. Whereas CTCs tend to be scarce in serum and plasma from cancer patient, abundant circulating nucleic acids can be detected in the same location. This fact, together with the genetic origin of cancer, stands out the relevance of circulating nucleic acids and shed light into the role of nucleic acids as drivers of metastasis, a recently discovered phenomenon called Genometastasis. This innovative theory supports the transfer of oncogenes from cancer cells to normal and susceptible cells located in distant target organs through circulatory system. What is more, many biological processes haven been described to deliver and secrete circulating nucleic acids into the circulation which can allow such horizontal transfer of oncogenes. In this review, we focus not only on these mechanisms but also we demonstrate its putative role in cancer propagation and give insights about possible therapeutic strategies based on this theory. Our objective is to demonstrate how findings about cell-to-cell communications and previous results can agree with this unprecedented theory.

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Revisiting Seed and Soil: Examining the Primary Tumor and Cancer Cell Foraging in Metastasis

Cited by 82 publications

References 71 publications

Polyploid giant cancer cells: Unrecognized actuators of tumorigenesis, metastasis, and resistance

Polyploid giant cancer cells: Unrecognized actuators of tumorigenesis, metastasis, and resistance

The two faces of enhanced stroma: Stroma acts as a tumor promoter and a steric obstacle

Further the liquid biopsy: Gathering pieces of the puzzle of genometastasis theory

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