Cancer stem cells, or tumor-initiating cells ), are becoming more and more popular in cancer treatment because they can spread throughout the body and result in metastasis, which can lead to cancerous tumors at other sites. Additionally, these cells might result in chemotherapy resistance.
The prognosis for pancreatic ductal adenocarcinoma ( PDAC ) cancer is not good. In this type of cancer, metastasis is a particularly serious issue. Although the tumor-initiating cells are linked to the development of some cancers, little is known about their precise function, distinctive characteristics, and the underlying signaling pathways by which they act in pancreatic adenocarcinoma. It is also unknown whether eliminating these PDAC-positive cells will have any therapeutic effects. Epithelial-mesenchymal transition( EMT)- like cells dispersed in tumors have metastatic and tumorigenic capabilities, making such EMT populations suitable candidates for tumor initiation in PDAC, according to prior research. A class of cell surface markers known as receptor tyrosine kinases( RTKs ) whose aberrant activation promotes the development of cancer. ROR1 in particular is an RTK that has been linked to numerous human cancers.
A subpopulation of partial EMT-like cells expressing ROR1 can now promote hyperproliferation in pancreatic cancer and result in metastasis, according to research from Japan. The group’s findings were just recently released on April 25, 2023, in The EMBO Journal. We wanted to understand the mechanism by which tumor-initiating cells act as cancer buds, leading to the design of new anti-cancer drugs, according to Masaya Yamazaki, Dr., who collaborated on this study with a group of researchers at University of Kumamoto under the direction of Professor Kazuyan Yamagata. So, at the single-cell level, we first looked into the cellular diversity within PDAC.
The team used a variety of methods, including single-cell RNA sequencing and the use of human PDAC xenografts, which involve transplanting human cancerous tissue into mice, in an effort to identify tumor – initiating cells. The researchers discovered that pancreatic cells with high ROR1 levels were more effective at producing cancerous tissue when transplanted into mice. Additionally, they discovered that ROR1high cells are common in metastatic lesions, indicating that they may have been the source of metastases. ROR1high cells also played a role in cancer relapse following chemotherapy. It’s interesting to note that inhibiting ROR1 expression during chemotherapy reduced the recurrence. As he elaborates on the study’s highlights, Dr. Yamazaki notes that” ROR1 is a characteristic marker of partial EMT-like cells localized in pancreatic tumor tissue, and high expression thereof drives tumorigenicity, intratumor heterogeneity and tumor progression.”
The discovery that ROR1 induces the expression of the protein Aurora kinase B, which is known to hasten tumor proliferation, was confirmed by the researchers as they went into more detail about its function at the molecular level. Additionally, the team found that Yes-associated protein ( YAP ) and bromodomains with 4 ( BRD4 ) axis are elements in the control of ROR1 gene expression. The group suggested using BET inhibitors as a therapeutic strategy to target ROR1 based on the findings of these studies.
The team is certain that their research has paved the way for future drug discovery and improved pancreatic cancer therapy approaches.
These findings imply the significance of researching ROR1 in order to comprehend its part in the pathogenesis of PDAC and other cancers.
Masaya Yamazaki, Dr.