LOR-1 belongs to a family of enzymes called Lysyl Oxidases, which participate in the creation of collagen fiber networks in the intercellular medium
Researchers at the Technion discovered a connection between the expression of the Lysyl Oxidase Related Protein-1 (LOR-1) protein and the malignancy and metastasis of breast cancer cells. The researchers, Professor Gera Neufeld and research student Gal Akiri from the Faculty of Biology at the Technion, explain that LOR-1 belongs to a family of enzymes called Lysyl Oxidases, which participate in the formation of collagen fiber networks in the intercellular medium. Collagen, the most common protein in the body, is one of the most important components of the extracellular material and is a skeletal protein.
It turned out that LOR-1 is expressed at a high level in breast cancer cells that have the ability to send metastases, but is not expressed in breast cancer cells that do not have the ability to send metastases. The researchers found that in tumors that were genetically engineered to express a high level of LOR-1, there is a high incidence of fibrotic foci, tumor areas with a higher than normal concentration of collagen fibers, and that between the tumor cells there is a much higher concentration of collagen fibers. At the same time, it turned out that those tumors, which develop from breast cancer cells that produce recombinant LOR-1, became more malignant. The tumor cells acquired invasive properties, which allowed them to penetrate blood vessels (see photo) and nerves. These features are characteristic of malignant cancer cells, which are capable of sending metastases to distant organs.
It is known in the scientific literature that the presence of fibrotic foci in human breast cancer tumors characterizes malignant tumors capable of sending metastases. This observation appears to be a paradox, since the proliferation of cancer cells is usually accompanied by the breakdown of the extracellular material. The creation of a dense network of collagen apparently makes it difficult to break down the extracellular material and is supposed to slow down the rate of spread of cancerous tumors. It turns out that high-level expression of LOR-1 simultaneously causes the creation of a network of collagen fibers and an increase in tumor penetration, thereby mimicking the phenomena observed in human breast cancer tumors.
In addition, the researchers found a high degree of correlation between the expression level of the LOR-1 protein and the degree of malignancy of human breast cancer tumors. It turned out that the protein is expressed in every normal breast in the ducts of the mammary glands, probably because in the vicinity of the ducts there is a factor that stimulates the creation of LOR-1 naturally. In the first stage of the development of an invasive tumor, where the cells come out of the ducts and the degree of malignancy is still low, the cells lose their protein expression. However, at a more advanced stage of tumor spread, when it acquires highly malignant characteristics, the LOR-1 protein is expressed in the tumor cells at a high level.
The researchers hypothesize that the location where LOR-1 is expressed is what determines its interactions with the environment and therefore its effect on the progression of the malignant tumor. As long as LOR-1 is located in the milk ducts, it does not cause cancerous effects. But when LOR-1 is expressed in cancer cells, which have already migrated outside the milk ducts, in a location where it should not be found naturally, it causes a massive deposition of collagen in the environment of the cancer tumor. The collagen fiber-rich environment appears to support tumor spread by a mechanism that has yet to be identified.
The research, which was published in the journal Cancer Research, was done in collaboration with the laboratory of Professor Michal Naeman from the Department of Biological Control at the Weizmann Institute and Dr. Edmond Savo from the Department of Pathology at the Carmel Medical Center.
