St Vincent’s Institute of Medical Research – 1989
1989 – $610,000 research grant
Research Institution: St Vincent’s Institute of Medical Research, Fitzroy, Victoria
Director of Research: Professor T (Jack) Martin
Cancer Type: Breast cancer
Feature Outcome:
The Institute’s studies have unravelled the communication network between breast cancer cells and cells within bone that ultimately result in bone destruction.
Research Focus:
Understanding how breast cancers contribute to bone destruction.
Research Background / Overview:
Breast cancers have a propensity to spread and establish in bone, causing considerable pain and pathological fractures. The Institute’s focus is to limit the spread and growth of breast cancers to bone.
Further Key Outcomes:
One principal factor that is expressed by breast cancers is a protein, called parathyroid hormone-related protein (PTHrP), which the Institute discovered over 10 years ago and is expressed by 80% of breast cancers. We have determined a major action for PTHrP expression by breast cancers when they grow in bone, in that production of PTHrP by breast cancer cells aids in the establishment of the tumour at this site. Although breast cancers alone do not have the capacity to degrade bone or directly stimulate the osteoclast (bone destroying cells) to degrade bone, PTHrP expressed by the cancer cell induces bone breakdown through an intermediate cell in bone.
The Institute’s studies have unravelled the communication network between breast cancer cells and cells within bone that ultimately results in bone destruction. The deciphering of this communication network has now realized several sites for intervention therapies – i) PTHrP, made by the breast cancer cell, ii) the PTHrP-stimulated factor RANKL, which is made by the osteoblast and is essential for stimulating the bone degrading cells, and iii) the growth factors released by bone in response to its destruction that facilitate tumour growth and expansion. Using appropriate models the Institute has validated some of these potential sites for intervention.
It has also established new roles for several factors involved in breast cancer progression, and determined how these factors are transported within the cell. These proteins are only active various compartments within a cell, and they require the use of intracellular railroads and locomotives to move proteins within the cell so that they are active at various stations or are quiescent in a siding. The Institute’s comprehension of this transport system has now identified new targets that are instructive in the design of new therapies to limit breast cancer cell growth.
