Urokinase Plasminogen Activator (uPA) and its Receptor uPAR

The Importance of Cell Movements

In Development

Early embryogenesis

Organ & tissue development

Organ & tissue remodeling throughout life

In defense & disease

Immune responses

Wound healing

Invasion & metastasis

Figure 14.24 The Biology of Cancer (© Garland Science 2007)

Hepatacyte Growth Factor (HGF) is a Powerful Inducer of Epithelial Cell Motility

Figure 14.23b The Biology of Cancer (© Garland Science 2007)

EGF Secreted by Mθs Induces Motility in Breast Carcinoma

Cells Recall:

filopodium

Rho Family Small G Proteins Play Central Roles in Cell Motility and Invasiness

Rac, Cdc42, Rho and their GEFs (eg Tiam1 Rac) are all involved in the orchestration of extension/sensing/contraction and MMP secretion that are involved in the movement of cells across surfaces.

A role for Rho proteins is demonstrated by studies of melanoma.

The Lymphatic System

Figure 14.41a The Biology of Cancer (© Garland Science 2007)

Metastasis to draining lymph node

Draining Lymph Nodes Can be Destinations for Metastatic Cells

Figure 14.42 The Biology of Cancer (© Garland Science 2007)

The ‘Seed and Soil’ Principle – Some Tissues are More Susceptible to Colonization by Particular Tumors Than Others

Figure 14.44 The Biology of Cancer (© Garland Science 2007)

Figure 14.46 The Biology of Cancer (© Garland Science 2007)

Breast Cancer Tends to be Osteolytic & Prostate Cancer Tends to be Osteoblastic

Figure 14.48 The Biology of Cancer (© Garland Science 2007)

The Osteoblastic Cascade

Table 14.4 The Biology of Cancer (© Garland Science 2007)

Figure 14.50a The Biology of Cancer (© Garland Science 2007)

Cytokeratin-free Bone Marrow Augurs Well

Figure 14.51a The Biology of Cancer (© Garland Science 2007)

Gene Expression Signatures Show Some Promise as Prognostic Indicators

Instigators & Responders – Implications for Micrometastases

McCallister et al., Cell 133:994 (2008)

Figure 14.53 The Biology of Cancer (© Garland Science 2007)