Tumour-educated macrophages promote tumour progression and metastasis

Evidence from clinical and experimental studies indicates that macrophages promote solid-tumour progression and metastasis. Macrophages are educated by the tumour microenvironment, so that they adopt a trophic role that facilitates angiogenesis, matrix breakdown and tumour-cell motility — all of which are elements of the metastatic process. During an inflammatory response, macrophages also produce many compounds — ranging from mutagenic oxygen and nitrogen radicals to angiogenic factors — that can contribute to cancer initiation and promotion. Macrophages therefore represent an important drug target for cancer prevention and cure. [1]

Epithelial–mesenchymal transitions in tumour progression

Without epithelial–mesenchymal transitions, in which polarized epithelial cells are converted into motile cells, multicellular organisms would be incapable of getting past the blastula stage of embryonic development. However, this important developmental programme has a more sinister role in tumour progression. Epithelial–mesenchymal transition provides a new basis for understanding the progression of carcinoma towards dedifferentiated and more malignant states. [2]

Tumour progression and the nature of cancer

The nature of neoplasia and its sometime end result, cancer, has been studied by exposition and explanation of the sequential lesions of tumour progression. Neoplastic lesions were divided into four classes on the basis of growth characteristics and whether lesional growth is confined to one or more tissue compartments. Class IA, the initial lesion, an orderly, probably clonal growth, usually differentiates and disappears. Class IB: Failure to differentiate accompanied by disorderly growth. Class IC: Randomly dispersed atypical cells, constituting a precursor state. Class II, intermediate lesions, apparently arising from the atypical cells, show temporally unrestricted growth within the tissue compartment of origin. Class III lesions, primary invasive cancers, show temporally unrestricted growth in two or more tissue compartments and metastasise along different paths, a property associated with extracellular matrix interaction. The metastatic pathways may result from different subsets of cells in the primary cancer. Class IV lesions are the metastases. It was concluded that, all neoplasms develop in the same way, have the same general behavioural characteristics, and, when malignant, all interact with the extracellular matrix of the primary and the secondary sites. The origins and development of cancer are considered to be pluralistic and not due to a discrete change in a cell, whose progeny, as a result of that discrete change, carries all of the information required to explain the almost limitless events of a neoplastic system. [3]

Dissecting Biology of Solid Tumour: The Microenvironment and Cancer Progression

Focus on cancer therapy is experiencing a major paradigm shift from ways of attacking tumor cells to a strategy for specifically targeting the tumor microenvironment (TME). This approach requires a comprehensive understanding of roles of each component of the tumor environment. A description of the tumor microenvironment and its impact on tumor progression is presented here. Available studies indicate that both tumor/epithelial and stroma characteristics play important roles in cancer progression. Details of this work show that different components of the tumor microenvironment contribute towards cancer progression and clearly suggest a role for use of combination therapies for tight tumor control. [4]

KRAS Mutation is a Local Tumour Event and Not a Field Change in Pancreatobiliary Tumours

Background: KRAS mutation (KRM) is the earliest, most common mutation in pancreatic cancer. Accurate assessment of tumour KRM status in pancreatobiiary tumours is relevant in an era of targeted molecular therapies.

Aim: To assess KRM in tumour and non-tumourous margin tissue in patients undergoing a pancreatic resection.

Study Design: Original research, retrospective review of prospectively collected specimens.

Place and Duration of Study: Patients who had undergone pancreaticoduodenectomy and distal pancreatic resection at the Royal Adelaide Hospital from 2011-2012 were consented for the study.

Methods: Patient demographics, background history and tumour details were collated. Tumour tissue and margin areas were macrodissected from FFPE tissue sections following identification by a pathologist. DNA was prepared from the tissue using the QIAamp FFPE Tissue kit (Qiagen GmbH, Hilden Germany). KRM at codons 12 and 13 was assessed using SNaPShot TM (Applied Biosystems, Warrington UK) in tumour tissue and non-tumourous margin tissue.

Fourteen patients were included in the study. The median age of the patients in the study was 68 (range 57-86) years. The M : F ratio was 8 : 6.

Results: Twelve patients had adenocarcinomas (5 pancreatic; 4 ampullary, 3 biliary) and two had benign mucinous tumours. Six patients with adenocarcinomas had KRM (5@codon 12 and 1@codon 13). Margin tissue was negative for KRM in all the tested patients (p<0.016 Fisher) particularly, in those with tumour KRM.

Tumours with KRM were associated with larger tumours 30(22-65) mm vs 20(15-35) mm [median(range)](p = .045 – MW-U). Nodal disease occurred in 6/6 with KRM vs 2/6 without KRM (p = .61 – Fisher).

Conclusions: KRM is a local tumour event and not a field change. This suggests that testing for KRM should be reliant on tumour tissue and not surrounding normal margin tissue. KRM was associated with larger malignant tumours and a trend towards nodal disease. [5]


[1] Pollard, J.W., 2004. Tumour-educated macrophages promote tumour progression and metastasis. Nature Reviews Cancer, 4(1), pp.71-78.

[2] Thiery, J.P., 2002. Epithelial–mesenchymal transitions in tumour progression. Nature reviews cancer, 2(6), pp.442-454.

[3] Clark, W.H., 1991. Tumour progression and the nature of cancer. British journal of cancer, 64(4), pp.631-644.

[4] Omabe, M. and Onyekachi, O.B., 2013. Dissecting Biology of Solid Tumour: The Microenvironment and Cancer Progression. Journal of Advances in Medicine and Medical Research, pp.1786-1797.

[5] Chandrasegaram, M.D., Chen, D.Y., Tan, C.P., Neo, E.L., Dolan, P.M., Chen, J.W., Brooke-Smith, M.E., Cheetham, G., Ruszkiewicz, A. and Worthley, C.S., 2013. KRAS mutation is a local tumour event and not a field change in pancreatobiliary tumours. Journal of Advances in Medicine and Medical Research, pp.2069-2075.

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