Introduction

Kaposi's sarcoma (KS) is the most common cancer arising in patients with acquired immunodeficiency syndrome (AIDS). KS is a multifocal neovascular tumor that most often manifests with skin lesions, although involvement of the oral mucosa, lymph nodes, and visceral organs is not uncommon. The recent introduction of highly active anti-retroviral therapy (HAART) has witnessed a dramatic decrease in the proportion of new AIDS-defining KS cases as well as a regression in the size of existing KS lesions. However, in parts of the developing world, KS has tragically emerged as one of the most frequent cancers among children and adult men, and it can be an aggressive disease that remains a significant cause of morbidity and mortality among the AIDS population [1].

The clinical course of AIDS-related KS is highly variable, ranging from minimal stable disease to explosive growth. In early-stage KS (also known as patch stage), dermal lesions are composed of small, irregular, endothe-lium-lined spaces that surround normal blood vessels, with perivascular infiltrates of lymphocytes and plasma cells. As the disease progresses into the plaque stage, the tumor (or spindle) cells form slit-like, erythrocyte-replete vascular channels that expand throughout the dermis. In late (or nodular) stage lesions, the dermis is replaced by sheets of spindle cells with interspersed vascular spaces that give the lesion the appearance of a honeycomb. More aggressive lesions are characterized by mitotic events and cellular atypia [2].

The dominant cell of KS lesions, the spindle cell, is believed to be of endothelial origin, although the precise histogenesis of these cells remains in debate. While not fully transformed, the KS spindle cell elaborates a variety of proinflammatory and angiogenic factors believed to be essential for the development of KS. Recent data support the

Autocrine Cycle

Autocrine growth factor/chemokine stimulation

Chemokine receptor

Secretion of angiogenic growth factors and cytokines

Autocrine growth factor/chemokine stimulation

Chemokine receptor

Secretion of angiogenic growth factors and cytokines

Growth factor receptor

Paracrine growth factor stimulation

Growth factor receptor

Paracrine growth factor stimulation

Paracrine recruitment of endothelial and inflammatory cells

Figure 1 Autocrine and paracrine growth factor cycles promoted by the Kaposi's sarcoma spindle cell. The KS spindle cell, believed to be of endothelial origin, is the driving force of KS with its secreted growth factors and cytokines sustaining its own proliferation while recruiting the remaining cell types in a paracrine fashion. (see color insert)

Paracrine recruitment of endothelial and inflammatory cells

Figure 1 Autocrine and paracrine growth factor cycles promoted by the Kaposi's sarcoma spindle cell. The KS spindle cell, believed to be of endothelial origin, is the driving force of KS with its secreted growth factors and cytokines sustaining its own proliferation while recruiting the remaining cell types in a paracrine fashion. (see color insert)

role of the spindle cell as the driving force of KS pathogenesis (Figure 1), with its secreted products responsible for the recruitment of the remaining cell types in a paracrine fashion [3]. However, the mechanism as to what initiates spindle cell formation and how secreted growth factors and cytokines sustain spindle cell growth is still poorly understood.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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