Nature: The first cancer metastasis map was published involving 500 human cancer cell lineages from 21 cancer species

Source: A recent study by scientists at the Massachusetts Institute of Technology-Harvard Broad Institute showed that it is possible to predict the metastasis of human cancer cells in animal models.
study, published in the journal Nature on December 9, suggests that whether, to what extent, and to which organ a cancer spreads depends on many genetic and clinical factors.
team gathered more than 500 human cancer cell line and metastasis-related features to create metastasis Map, the first ever map of how different cancers spread.
Source: Nature This resource could help scientists discover new details about what drives metastasis, why some cancers spread more violently than others, and how new cancer drugs can potentially slow or stop this deadly process.
specifically,
Xin Jin, a researcher at the Broad Institute who led the study, and colleagues attached unique DNA barcode molecules to each of the 500 cancer cell lines spanning 21 cancer species, enabling them to identify and track cancer cells.
then injected different combinations of cell line into the mouse's circulatory system and monitored the spread of cells.
5 weeks, samples were collected from the brain, lungs, liver, kidneys, and bone to determine which cell line settled on which organ.
team found that more than 200 cell line survived and metastasised in mice.
they identified key characteristics associated with tumor diffusion, including tumor type, origin, and age of cell-sourced patients, and used this information to generate MetMap (Figure 1).
Figure 1. The MetMap (Source: Nature) mapping 500 human cancer cell lines, in which the feasibility and reliability of monitoring the growth of cancer cells in different tissues of mice with bar code technology in the body showed that HCC1954 had the highest detection rate in the brain, while extracranial metastases were dominated by MDAMB231.
it is worth noting that the cancer cell line, numbered BT20, is detected in multiple organs but has low abundance in all organs, reflecting its ability to plant but not expand (Figure 2).
2. In vivo transfer potential mapping of cell pools marked by barcodes.
, including myself, at first, believed it would work, " says Jin, a professor at the time.
found that it was powerful, generating unexpected information about what makes different cancers adapt to different organ environments.
to prove the value of their data, scientists studied a breast cancer further, and MetMap showed a trend toward the brain.
They compared the genomes of these cell line to those of non-metastasis breast cancer cell line and found some differences that promote the spread of cancer cells to the brain: PIK3CA was the most relevant at the so many cell mutation levels: 4 out of 7 brain metastasis cell lineages contained PIK3CA mutations, while 14 non-metastasis or weak metastasis cell lineages The mutation is 0 (pseudo-discovery rate, FDR=0.0034) (Figure 4a); the fifth cell line HCC70 has a functionally missing mutation in PTEN; and PI3K is the main downstream medium of ERBB2 (also known as HER2), which is reported to be associated with human brain transfer itself.
, two brain metastasis cell linees, JIMT1 and HCC195, also contain typical ERBB2 gene amplification (Figure 3).
3. Genetically related studies of brain metastasis potential for basal-like breast cancer (Source: Nature) At the DNA copy number level, they observed an association between metastasis potential and chromosomal 8p12-8p21.2 (called 8p) deficiency (FDR=0.0017) (Figure 4b).
five out of seven brain metastasis breast cancer cells are missing in this region, compared with 0 in 14 non-metastasis cell line.
is also noteworthy that key changes in the lipid metabolism of breast cancer cells (Figure 4c-e) enable them to survive in the micro-environment of the brain, suggesting that future treatments could disrupt lipid metabolism, potentially slowing this metastasis.
4. Relationship between changes in lipid metabolism in basal-like breast cancer and brain metastasis potential.
(Source: Nature) further studies have found that SREBF1 is most associated with brain metastasis dependence.
SREBF1 is the key transcription factor for the lipid synthesis downstream of the pilot PI3K path.
brain metastasis cell line growth is selectively needed for SREBF1 compared to breast cancer cell line with low or no brain metastasis potential.
this association is unique to the brain because there is no link between SREBF1 and metastasis to other organs (Figure 4f).
, a series of genetic, metabolic, transcriptomic and functional genomics evidence showed a link between SREBF1-mediated lipid metabolism and brain metastasis.
Golub, chief scientific officer at Broad and a researcher at the Dana Farber Cancer Institute, said: "We want to contribute to the field of cancer metastasis by creating high-quality, large-scale, basic data sets that are available free of charge around the world.
"MetMap website resources are available for access.
: 1 s map show how cancer cells through spread the body (Medical Press) 2 s Xin Jin et al. A metastasis map of human cancer cell lines, Nature (2020). DOI: 10.1038/s41586-020-2969-2