A New Study on PDX Models Being Applied to Describe The Proteome of The Tumor Microenvironment

The team led by researchers from New York University and Washington University recently published a new study on Science Signaling, which is related to the PDX models being applied to describe the proteome of breast tumors.

SHIRLEY – SEP 30TH, 2017 – The team led by researchers from New York University and Washington University recently published a new study on Science Signaling, which is related to the PDX models being applied to describe the proteome of breast tumors.

Tumor microenvironment has been an area of interest in research for a really long time, but only a few large-scale proteomics that works on this tissue. However, due to a variety of reasons which make it difficult to distinguish between stromal and tumor tissue and gather enough samples to enable a useful analysis. Jason Held, the assistant professor at WUSTL and senior author for this study, transplanting patient-derived xenografts (PDX) localized in the mouse and colonizing the juvenile matrix with his team while allowing the molecular identification of human proteins in the microenvironment from mouse proteins in tumors.

The researchers studied seven kinds of breast cancer PDX models, which represent basal, HER2 enrichment, lumens and low-density subtypes. They implanted each patient tumor into three mice, each giving them three biological replicates. After developing tumors in mice, they were dissected and used to observe the matrix and tumor proteome using a mass spectrum of 10-plexTM T isoforms.

However, the proteome changed from each tumor is very noticeable. Comprehensive analysis of tumors and stromal proteins, along with the comparison of these xenograft models shows that the known signs of cancer have multiple effects on the establishment and maintenance of the microenvironment niche of the tumor.

The researchers also used data from the National Cancer Institute’s Cancer Genome Atlas project to determine whether the changes they observed in the stroma of the PDX models were consistent with the stroma changes in the tumor microenvironment of primary tumors.

Since the tumor tissue belongs different organisms (human or mouse), they are able to distinguish both by recognizing the measured peptide as being either mouse or human. In addition, as scientists were able to implant different tumors into multiple mice, which makes it possible to replicate their study to determine whether the observed phenomenon was replicated in multiple subjects. The regulation of PDX matrix proteins through breast tumors is extensive, with 35% of the matrix proteome being consistently altered by different animals and passages. The proteins in the matrix are differentially regulated into six marks, including known and previously unrecognized tumor invasion and colonization contributors.

Although they are unable to distinguish between tumor and stroma tissue in TCGA data, they can approach by observing specific proteins that are known to be expressed primarily in the stroma and are usually not present in the tumor itself. They found that there was a high correlation between their data and the protein between the mRNA and the proteomics data generated by TCGA, indicating that the PDX model and primary tumor affected its microenvironment in a similar method.

Except for the insight for the interaction between the tumor and the surrounding matrix, this study also reviewed the potential application of tumor treatment.

“The implication is that these [stroma protein] changes are probably very important for tumor growth,” Held said. “These tumors are kind of finding their way around, and they have to highjack the stroma in order to make it suitable for growth. People aren’t thinking too much right now about how to drug the stroma, but here we are providing molecular information that could be potentially useful for [such an effort.]”

Held and his team already started the further study. They aim to figure out how to drug the stroma and estimate which stromal proteins may be important for tumor growth with this information. What’s more, discovering strategies that may co-target tumors and stroma.

About patient-derived xenograft cell lines offered by Creative Bioarray

Creative Bioarray is well equipped with advanced research platforms and exquisite technical team for establishing diverse and reliable PDX models, either subcutaneous tumor xenografts or orthotopic human tumor xenograft models, which targets the following categories, but is not limited to:

. Breast Cancer
. Lung Cancer
. Gastric Cancer
. Colorectal Cancer
. Pancreatic Cancer

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