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▎Edited by WuXi AppTec's content team The metastasis of cancer cells to other organs is the main cause of cancer-related deaths.
Most breast cancer metastasizes to the bones, and in more than two-thirds of cases, metastasis is not limited to the bones, but also spreads to other organs and eventually leads to death.
Due to the lack of corresponding preclinical models, how cancer cells grow in bones and spread to other tissues is still an unsolved mystery.
Recently, two studies led by Professor Zhang Xiang, a Chinese scientist at Baylor College of Medicine, provided clues to the mystery.
The study explains why despite targeted treatment, estrogen receptor-positive (ER+) breast cancer sometimes metastasizes to the bones to re-grow and spread to other tissues.
The research results also point out promising candidate targets for treatment.
▲Professor Zhang Xiang, the corresponding author of the paper (photo source: Baylor College of Medicine official website) In these two papers, Professor Zhang Xiang and his colleagues used a series of previously developed models to study the interaction between cancer cells and bones at single-cell resolution.
Function to observe what happens when ER+ breast cancer cells metastasize to the bone? What helps them resist endocrine therapy and enhance the ability to transfer to other organs? Research results published in the journal Developmental Cell show that the bone micrometastases surrounding ER+ breast cancer cells reduce the expression of ER in these cells, leading to resistance to endocrine therapy.
Research published in the journal Cell shows that the bone microenvironment triggers the reprogramming of cancer cells and promotes their ability to metastasize or spread to other tissues.
Specifically, using animal models that include patient tumor samples, researchers found that when ER+ breast cancer cells are located in the bones, the expression and activity of ER in bone metastatic cancer cells are temporarily reduced, which makes them useful for endocrine therapies that directly target ER.
Not so sensitive.
The research team determined that osteoblasts, the cells that make new bone, promote this change in cancer cells by releasing factors and direct physical interaction with the cells.
Studies have proved that this process is independent of clonal selection and represents EZH2-mediated epigenome reprogramming.
▲The metabolic pathway mediated by EZH2 in the bone microenvironment affects ER signal expression and produces tolerance to endocrine therapy (picture source: reference [2]) It is worth noting that the interaction with osteoblasts also triggers Changes in gene expression make cancer cells have stem cell-like characteristics, such as uncontrolled self-renewal and differentiation into various cell types.
It is these characteristics that make cancer cells more capable of producing new metastases.
The research team identified some metabolic pathways that are altered by the bone microenvironment in cancer cells.
Among these pathways, EZH2-mediated pathways drive ER+ breast cancer cells to a stem cell-like state.
Inhibition of EZH2 can reverse resistance to endocrine therapy.
▲Direct and indirect metastasis of cancer cells (picture source: Reference [3]) Research also shows that the bone microenvironment is conducive to the further metastasis of breast cancer and the establishment of multiple organ secondary metastasis.
This role in promoting metastasis is driven by epigenetic reprogramming.
EZH2 is a methyltransferase, which is involved in the regulation of development and differentiation through epigenetic maintenance.
The enhancement of EZH2 activity mediates cancer cells to increase stem cell stemness and metastasis ability.
The same findings also apply to populations of single-cell origin, indicating a different mechanism from clonal selection.
In addition, experimental results show that the bone microenvironment can also lead to other types of cancer, such as the further metastasis of prostate cancer cells.
▲Dr.
Weijie Zhang, one of the main authors of the study (picture source: Baylor College of Medicine official website) "We are studying whether bone metastases are more likely to spread to other organs than the primary tumor," the co-first author of the work Dr.
Weijie Zhang said, “We found that the bone microenvironment is like a'power station' for cancer cells, enhancing their ability to spread to other organs.
That is, many metastases may not be initiated by the primary tumor, but by other The further spread of metastases was initiated.
” “In short, these studies revealed the previously unrecognized role of the bone microenvironment in the progression of metastasis, and clarified the reprogramming process that drives the end-stage and multi-organ metastasis.
The clinical mystery of ER+ breast cancer that is still metastatic and recurring provides a new perspective.
” Professor Zhang Xiang concluded.
Source of title picture: 123RF References: [1] Bone microenvironment fosters breast cancer metastatic behavior.
Retrieved April 19, 2021, from behavior[2] Bado, IL, et al.
(2021).
The bone microenvironment increases phenotypic plasticity of ER+ breast cancer cells.
Developmental Cell, 56(8), 1100–1117.
e9.
https://doi.
org/10.
1016 /j.
devcel.
2021.
03.
008[3] Zhang, W.
, et al.
(2021).
The bone microenvironment invigorates metastatic seeds for further dissemination.
Cell, 184(9), 2471–2486.
e20.
https:// doi.
org/10.
1016/j.
cell.
2021.
03.
011
Most breast cancer metastasizes to the bones, and in more than two-thirds of cases, metastasis is not limited to the bones, but also spreads to other organs and eventually leads to death.
Due to the lack of corresponding preclinical models, how cancer cells grow in bones and spread to other tissues is still an unsolved mystery.
Recently, two studies led by Professor Zhang Xiang, a Chinese scientist at Baylor College of Medicine, provided clues to the mystery.
The study explains why despite targeted treatment, estrogen receptor-positive (ER+) breast cancer sometimes metastasizes to the bones to re-grow and spread to other tissues.
The research results also point out promising candidate targets for treatment.
▲Professor Zhang Xiang, the corresponding author of the paper (photo source: Baylor College of Medicine official website) In these two papers, Professor Zhang Xiang and his colleagues used a series of previously developed models to study the interaction between cancer cells and bones at single-cell resolution.
Function to observe what happens when ER+ breast cancer cells metastasize to the bone? What helps them resist endocrine therapy and enhance the ability to transfer to other organs? Research results published in the journal Developmental Cell show that the bone micrometastases surrounding ER+ breast cancer cells reduce the expression of ER in these cells, leading to resistance to endocrine therapy.
Research published in the journal Cell shows that the bone microenvironment triggers the reprogramming of cancer cells and promotes their ability to metastasize or spread to other tissues.
Specifically, using animal models that include patient tumor samples, researchers found that when ER+ breast cancer cells are located in the bones, the expression and activity of ER in bone metastatic cancer cells are temporarily reduced, which makes them useful for endocrine therapies that directly target ER.
Not so sensitive.
The research team determined that osteoblasts, the cells that make new bone, promote this change in cancer cells by releasing factors and direct physical interaction with the cells.
Studies have proved that this process is independent of clonal selection and represents EZH2-mediated epigenome reprogramming.
▲The metabolic pathway mediated by EZH2 in the bone microenvironment affects ER signal expression and produces tolerance to endocrine therapy (picture source: reference [2]) It is worth noting that the interaction with osteoblasts also triggers Changes in gene expression make cancer cells have stem cell-like characteristics, such as uncontrolled self-renewal and differentiation into various cell types.
It is these characteristics that make cancer cells more capable of producing new metastases.
The research team identified some metabolic pathways that are altered by the bone microenvironment in cancer cells.
Among these pathways, EZH2-mediated pathways drive ER+ breast cancer cells to a stem cell-like state.
Inhibition of EZH2 can reverse resistance to endocrine therapy.
▲Direct and indirect metastasis of cancer cells (picture source: Reference [3]) Research also shows that the bone microenvironment is conducive to the further metastasis of breast cancer and the establishment of multiple organ secondary metastasis.
This role in promoting metastasis is driven by epigenetic reprogramming.
EZH2 is a methyltransferase, which is involved in the regulation of development and differentiation through epigenetic maintenance.
The enhancement of EZH2 activity mediates cancer cells to increase stem cell stemness and metastasis ability.
The same findings also apply to populations of single-cell origin, indicating a different mechanism from clonal selection.
In addition, experimental results show that the bone microenvironment can also lead to other types of cancer, such as the further metastasis of prostate cancer cells.
▲Dr.
Weijie Zhang, one of the main authors of the study (picture source: Baylor College of Medicine official website) "We are studying whether bone metastases are more likely to spread to other organs than the primary tumor," the co-first author of the work Dr.
Weijie Zhang said, “We found that the bone microenvironment is like a'power station' for cancer cells, enhancing their ability to spread to other organs.
That is, many metastases may not be initiated by the primary tumor, but by other The further spread of metastases was initiated.
” “In short, these studies revealed the previously unrecognized role of the bone microenvironment in the progression of metastasis, and clarified the reprogramming process that drives the end-stage and multi-organ metastasis.
The clinical mystery of ER+ breast cancer that is still metastatic and recurring provides a new perspective.
” Professor Zhang Xiang concluded.
Source of title picture: 123RF References: [1] Bone microenvironment fosters breast cancer metastatic behavior.
Retrieved April 19, 2021, from behavior[2] Bado, IL, et al.
(2021).
The bone microenvironment increases phenotypic plasticity of ER+ breast cancer cells.
Developmental Cell, 56(8), 1100–1117.
e9.
https://doi.
org/10.
1016 /j.
devcel.
2021.
03.
008[3] Zhang, W.
, et al.
(2021).
The bone microenvironment invigorates metastatic seeds for further dissemination.
Cell, 184(9), 2471–2486.
e20.
https:// doi.
org/10.
1016/j.
cell.
2021.
03.
011
