Advanced

Interactions between prostate cancer and bone marrow cells promote metastatic growth and invasion

Karlsson, Richard (2016) MOBT01 20161
Degree Projects in Molecular Biology
Popular Abstract
Interactions between Prostate Cancer and Bone Marrow Cells Promote Cancer Metastasis

Prostate cancer (PCa) results in death for around 300.000 men every year and is the fifth most dangerous form of cancer for this sex. Many treatments are available but when the cancer has metastasized to the bone marrow (BM) the outcome is rarely positive. In our newly developed molecule we have found a possibly potent weapon in the fight against PCa. This molecule serves as an inhibitor of a kinase that is very vital for metastatic progression of cancers and has been shown to reduce tumor growth in mice models.

PCa has a preference for metastasizing in the BM and the reasons for this have not yet been completely identified. BM is found inside the... (More)
Interactions between Prostate Cancer and Bone Marrow Cells Promote Cancer Metastasis

Prostate cancer (PCa) results in death for around 300.000 men every year and is the fifth most dangerous form of cancer for this sex. Many treatments are available but when the cancer has metastasized to the bone marrow (BM) the outcome is rarely positive. In our newly developed molecule we have found a possibly potent weapon in the fight against PCa. This molecule serves as an inhibitor of a kinase that is very vital for metastatic progression of cancers and has been shown to reduce tumor growth in mice models.

PCa has a preference for metastasizing in the BM and the reasons for this have not yet been completely identified. BM is found inside the bones and consists of an array different cell-types, such as the cells of the immune system and their precursors. These cells have been shown to aid PCa cells in grabbing a foothold in the BM as molecular interactions between the cells seem to stimulate PCa cells to increase their metastatic ability.

Kinases are enzymes that transfer a phosphate group from one molecule to another. The lipid kinase that we have been investigating is highly expressed in PCa cells and has been shown to be important for the ability of these cells to multiply and invade into other parts of the body. Indications that our lipid kinase can be activated by a cell membrane receptor made us want to investigate the link between these molecules in regards to PCa metastasis to the BM. When investigating tissue from patients with PCa we confirmed the link between them as high expression of both molecules correlates with metastasis. By using BM cells extracted from mice bones and growing them together with PCa cells in the lab we were able to recreate the environment that the PCa cells face in the BM and show that the BM cells did cause PCa cells to multiply faster. Expression of the lipid kinase and the cell membrane receptor was increased in some of these experiments and their expression does seem to be linked to one another.

We also showed that the specific inhibitor of our lipid kinase is restraining PCa metastasis, and this could potentially lead to increased survival for patients. When investigating cell cycle activity of PCa cells we found that when treated with the lipid kinase inhibitor, many PCa cells went into hibernation and did not complete the cell division cycle. When grown together with mice BM, an even large fraction of the treated cells were confined to hibernation. This means that the positive effect of our drug might be even more pronounced on PCa cells residing in the BM of patients than on cells in the lab.

All cells in a PCa cell line that you grow in a lab do not have the exact same properties. Some are more open to be influenced by other cells and have a higher ability to adapt and differentiate into various cell-types. By separating these cells from others we showed that they have a higher metastatic ability as they formed more colonies than the rest of the population. A higher colony formation ability can be seen as a higher capacity for tumor formation. These cells were also shown to multiply faster than the other cells.


Supervisor: Jenny L. Persson
Master Degree Project in Molecular Biology, 60 credits, 2016
Department of Biology, Lund University (Less)
Please use this url to cite or link to this publication:
author
Karlsson, Richard
supervisor
organization
course
MOBT01 20161
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8892803
date added to LUP
2016-10-03 15:02:42
date last changed
2016-10-03 15:02:42
@misc{8892803,
  author       = {Karlsson, Richard},
  language     = {eng},
  note         = {Student Paper},
  title        = {Interactions between prostate cancer and bone marrow cells promote metastatic growth and invasion},
  year         = {2016},
}