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Msg  30771 of 31044  at  10/21/2019 1:05:22 PM  by

moneyonomics

The following message was updated on 10/21/2019 1:08:47 PM.

Those new to Manocept Science. The future is slow to advance but if/when RA approved..if KS trials succeed .." The view of metastasis as a macrophage metabolic disease can provide novel insight for therapeutic management."

 
. Author manuscript; available in PMC 2014 Jan 1.
Published in final edited form as:
PMCID: PMC3597235
NIHMSID: NIHMS448949
PMID: 23237552

On the Origin of Cancer Metastasis

Abstract

Metastasis involves the spread of cancer cells from the primary tumor to surrounding tissues and to distant organs and is the primary cause of cancer morbidity and mortality. In order to complete the metastatic cascade, cancer cells must detach from the primary tumor, intravasate into the circulatory and lymphatic systems, evade immune attack, extravasate at distant capillary beds, and invade and proliferate in distant organs. Currently, several hypotheses have been advanced to explain the origin of cancer metastasis. These involve an epithelial mesenchymal transition, an accumulation of mutations in stem cells, a macrophage facilitation process, and a macrophage origin involving either transformation or fusion hybridization with neoplastic cells. Many of the properties of metastatic cancer cells are also seen in normal macrophages. A macrophage origin of metastasis can also explain the long-standing “seed and soil” hypothesis and the absence of metastasis in plant cancers. The view of metastasis as a macrophage metabolic disease can provide novel insight for therapeutic management.....

... 

XI. MANAGING METASTATIC CANCERS

As a metabolic disease, most if not all cancers can be managed by targeting those fuels necessary for their proliferation and survival. The goal is to first transition energy metabolism of all normal cells of the body to ketone bodies, which tumor cells cannot effectively use for energy. It is well documented that most tumor cells require glucose for energy through glycolysis.- Glutamine is also a major metabolic fuel for many cells of the immune system including macrophages.,, We recently showed that the simultaneous targeting of glucose and glutamine under calorie restriction could significantly reduce systemic metastatic cancer in the VM-M2 mouse model., Indeed, targeting these fuels was more effective in blocking metastasis than was using the well-known toxic chemotherapies methotrexate or cisplatin. Once metastatic cancer becomes recognized as a metabolic disease, new and less toxic solutions will emerge for effective management.

XII. CONCLUDING REMARKS

A transition from an epithelial cell to a mesenchymal cell is considered an underlying characteristic of metastasis. However, it is improbable that random mutations acquired through a Darwinian selection process could account for all of the myeloid-cell behaviors necessary for the completion of the metastatic cascade. As an alternative to a series of gain-of-function mutations and clonal selection, we propose that the metastatic mesenchymal phenotype arises initially from respiratory damage in macrophages or in epithelial-macrophage fusion hybrids, which is then followed by compensatory fermentation. This would produce the metastatic lesion images seen on PET. Inflammation and radiation damage enhances hybridization while also damaging mitochondrial function over time. It is our opinion that the myeloid origin of metastasis is the most compelling explanation for the origin of metastasis and tumor progression. We anticipate major advances in management of metastatic cancer once this explanation becomes more widely recognized."

 
 
 


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Msg # Subject Author Recs Date Posted
30772 Re: Those new to Manocept Science. The future is slow to advance but if/when RA approved..if KS trials succeed .." The view of metastasis as a macrophage metabolic disease can provide novel insight for therapeutic management." dadeo55 0 10/21/2019 2:36:19 PM


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