Analysis of the Molecular Crosstalk Between Tumor Cells and the Microenvironment in Lymphatic Metastasis
(2024) KIMM01 20241Department of Immunotechnology
Educational programmes, LTH
- Abstract
- Lymphatic metastasis is a critical determinant of poor prognosis in various human cancers, facilitating further dissemination through the vascular system. However, the absence of an appropriate murine model impedes the comprehensive study of lymphatic metastasis. To address this, the host laboratory employs the EO771 mouse mammary carcinoma model, which ectopically expresses the chemokine receptor, enhancing lymphatic metastasis in BL/6 mice. Unexpectedly, the host laboratory observed spontaneous upregulation of the glycoprotein in EO771 cells expressing one chemokine receptor. Subsequent in vivo experiments demonstrated that neither chemokine receptor nor glycoprotein alone suffices to induce lymphatic metastasis or tumor growth; only... (More)
- Lymphatic metastasis is a critical determinant of poor prognosis in various human cancers, facilitating further dissemination through the vascular system. However, the absence of an appropriate murine model impedes the comprehensive study of lymphatic metastasis. To address this, the host laboratory employs the EO771 mouse mammary carcinoma model, which ectopically expresses the chemokine receptor, enhancing lymphatic metastasis in BL/6 mice. Unexpectedly, the host laboratory observed spontaneous upregulation of the glycoprotein in EO771 cells expressing one chemokine receptor. Subsequent in vivo experiments demonstrated that neither chemokine receptor nor glycoprotein alone suffices to induce lymphatic metastasis or tumor growth; only their concurrent expression yields these outcomes. Moreover, tumors derived from EO771 cells co-expressing chemokine receptor and glycoprotein exhibited reduced infiltration of CD8+ T cells, suggesting that chemokine receptor and glycoprotein may modulate the tumor microenvironment directly or indirectly.
One hypothesis posits that glycoprotein expression might signify the selection of a differentiation variant with molecular characteristics conducive to lymphatic metastasis and chemokine receptor expression. This hypothesis was investigated through bulk RNA sequencing analysis. Additionally, single-cell RNA sequencing data from human primary triple-negative breast cancer (TNBC) were reanalyzed to explore potential similarities between human and mouse models. Notably, glycoprotein expression correlated positively with collagen expression in both EO771 cells and human TNBC, potentially contributing to tumor growth and lymphatic metastasis. However, interferon responses were downregulated in EO771 cells with glycoprotein expression, contrasting with upregulated responses in human primary tumors. This discrepancy may reflect interactions between tumor cells and other components of the human tumor microenvironment.
To ascertain whether glycoprotein drives these observed effects, in vivo study was conducted using chemokine receptor-positive EO771 cells overexpressing glycoprotein. However, the preliminary nature of these studies precluded definitive conclusions, potentially due to the high immunogenicity of the vector used. (Less) - Popular Abstract
- In the human body, tumor cells can spread from their original places to other parts of the body. For example, breast cancer cells can travel from the breast to other areas of the body, such as the brain, lungs, etc. Cancer cells can metastasize through two pathways, one is through the blood and the other is through the lymphatic system. The lymphatic system is an important way for the human body to resist external interference. Therefore, when cancer cells invade the lymphatic system, it may destroy the body's ability to fight cancer. Moreover, patients who get lymphatic metastasis have a hard time recovering from cancers.
But we don’t know much about how cancer invades the lymphatic system, mainly because we don’t have suitable... (More) - In the human body, tumor cells can spread from their original places to other parts of the body. For example, breast cancer cells can travel from the breast to other areas of the body, such as the brain, lungs, etc. Cancer cells can metastasize through two pathways, one is through the blood and the other is through the lymphatic system. The lymphatic system is an important way for the human body to resist external interference. Therefore, when cancer cells invade the lymphatic system, it may destroy the body's ability to fight cancer. Moreover, patients who get lymphatic metastasis have a hard time recovering from cancers.
But we don’t know much about how cancer invades the lymphatic system, mainly because we don’t have suitable experimental animals to study it. Due to ethical reasons, we cannot conduct research on humans. Because we need to let tumors grow in the human body if we study lymphatic metastasis in humans. Therefore, we need a suitable animal to study cancer lymphatic metastasis.
To overcome this problem, we engineered a type of mouse breast cancer cell called EO771. These cancer cells will express a target called CCR7 after being engineered, which helps the cancer cells find their way to the lymph nodes in the mouse. Another target called PDPN was also found on the cancer cells with the expression of CCR7 at the same time.
We tested whether the emergence of PDPN means that there is a specific type of mouse breast cancer cells that are particularly prone to metastasis into the lymphatic system. We used a technology called Bulk RNA Sequencing on mouse breast cancer cells. The results show that the emergence of PDPN is indeed accompanied by some characteristics that make cancer cells easier to metastasize to the lymphatics system. We also analyzed human breast cancer cells. The results showed that some of the results in human tumor cells were consistent with those in mice, but some of the results were the opposite. To be able to know the reasons, we need to do more experiments. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9160021
- author
- Wang, Zhi LU
- supervisor
- organization
- course
- KIMM01 20241
- year
- 2024
- type
- H2 - Master's Degree (Two Years)
- subject
- keywords
- Breast cancer, lymphatic metastasis, Bulk RNA sequencing, Collagens
- language
- English
- id
- 9160021
- date added to LUP
- 2024-06-09 13:38:15
- date last changed
- 2024-06-09 13:38:15
@misc{9160021,
abstract = {{Lymphatic metastasis is a critical determinant of poor prognosis in various human cancers, facilitating further dissemination through the vascular system. However, the absence of an appropriate murine model impedes the comprehensive study of lymphatic metastasis. To address this, the host laboratory employs the EO771 mouse mammary carcinoma model, which ectopically expresses the chemokine receptor, enhancing lymphatic metastasis in BL/6 mice. Unexpectedly, the host laboratory observed spontaneous upregulation of the glycoprotein in EO771 cells expressing one chemokine receptor. Subsequent in vivo experiments demonstrated that neither chemokine receptor nor glycoprotein alone suffices to induce lymphatic metastasis or tumor growth; only their concurrent expression yields these outcomes. Moreover, tumors derived from EO771 cells co-expressing chemokine receptor and glycoprotein exhibited reduced infiltration of CD8+ T cells, suggesting that chemokine receptor and glycoprotein may modulate the tumor microenvironment directly or indirectly.
One hypothesis posits that glycoprotein expression might signify the selection of a differentiation variant with molecular characteristics conducive to lymphatic metastasis and chemokine receptor expression. This hypothesis was investigated through bulk RNA sequencing analysis. Additionally, single-cell RNA sequencing data from human primary triple-negative breast cancer (TNBC) were reanalyzed to explore potential similarities between human and mouse models. Notably, glycoprotein expression correlated positively with collagen expression in both EO771 cells and human TNBC, potentially contributing to tumor growth and lymphatic metastasis. However, interferon responses were downregulated in EO771 cells with glycoprotein expression, contrasting with upregulated responses in human primary tumors. This discrepancy may reflect interactions between tumor cells and other components of the human tumor microenvironment.
To ascertain whether glycoprotein drives these observed effects, in vivo study was conducted using chemokine receptor-positive EO771 cells overexpressing glycoprotein. However, the preliminary nature of these studies precluded definitive conclusions, potentially due to the high immunogenicity of the vector used.}},
author = {{Wang, Zhi}},
language = {{eng}},
note = {{Student Paper}},
title = {{Analysis of the Molecular Crosstalk Between Tumor Cells and the Microenvironment in Lymphatic Metastasis}},
year = {{2024}},
}